EC 2.1.1.1     
Accepted name: nicotinamide N-methyltransferase
Reaction: S-adenosyl-L-methionine + nicotinamide = S-adenosyl-L-homocysteine + 1-methylnicotinamide
Other name(s): nicotinamide methyltransferase
Systematic name: S-adenosyl-L-methionine:nicotinamide N-methyltransferase
References:
1.  Cantoni, G.L. Methylation of nicotinamide with a soluble enzyme system from rat liver. J. Biol. Chem. 189 (1951) 203–216. [PMID: 14832232]
[EC 2.1.1.1 created 1961]
 
 
EC 2.1.1.2     
Accepted name: guanidinoacetate N-methyltransferase
Reaction: S-adenosyl-L-methionine + guanidinoacetate = S-adenosyl-L-homocysteine + creatine
Other name(s): GA methylpherase; guanidinoacetate methyltransferase; guanidinoacetate transmethylase; methionine-guanidinoacetic transmethylase; guanidoacetate methyltransferase
Systematic name: S-adenosyl-L-methionine:N-guanidinoacetate methyltransferase
References:
1.  Cantoni, G.L. and Scarano, E. The formation of S-adenosylhomocysteine in enzymatic transmethylation reactions. J. Am. Chem. Soc. 76 (1954) 4744.
2.  Cantoni, G.L. and Vignos, P.J. Enzymatic mechanism of creatine synthesis. J. Biol. Chem. 209 (1954) 647–659. [PMID: 13192118]
[EC 2.1.1.2 created 1961]
 
 
EC 2.1.1.3     
Accepted name: thetin—homocysteine S-methyltransferase
Reaction: dimethylsulfonioacetate + L-homocysteine = (methylsulfanyl)acetate + L-methionine
Glossary: thetin = sulfobetaine = dimethylsulfonioacetate
Other name(s): dimethylthetin-homocysteine methyltransferase; thetin-homocysteine methylpherase
Systematic name: dimethylsulfonioacetate:L-homocysteine S-methyltransferase
References:
1.  Klee, W.A., Richards, H.H. and Cantoni, G.L. The synthesis of methionine by enzymic transmethylation. VII. Existence of two separate homocysteine methylpherases on mammalian liver. Biochim. Biophys. Acta 54 (1961) 157–164. [PMID: 14456704]
2.  Maw, G.A. Thetin-homocysteine transmethylase. A preliminary manometric study of the enzyme from rat liver. Biochem. J. 63 (1956) 116–124. [PMID: 13315256]
3.  Maw, G.A. Thetin-homocysteine transmethylase. Some further characteristics of the enzyme from rat liver. Biochem. J. 70 (1958) 168–173. [PMID: 13584318]
[EC 2.1.1.3 created 1961]
 
 
EC 2.1.1.4     
Accepted name: acetylserotonin O-methyltransferase
Reaction: S-adenosyl-L-methionine + N-acetylserotonin = S-adenosyl-L-homocysteine + melatonin
Glossary: melatonin = N-acetyl-5-methoxytryptamine
serotonin = 5-hydroxytryptamine
tryptamine = 2-(1H-indol-3-yl)ethanamine
Other name(s): hydroxyindole methyltransferase; hydroxyindole O-methyltransferase; N-acetylserotonin O-methyltransferase; acetylserotonin methyltransferase
Systematic name: S-adenosyl-L-methionine:N-acetylserotonin O-methyltransferase
Comments: Some other hydroxyindoles also act as acceptor, but more slowly.
References:
1.  Axelrod, J. and Weissbach, H. Purification and properties of hydroxyindole-O-methyl transferase. J. Biol. Chem. 236 (1961) 211–213. [PMID: 13685335]
[EC 2.1.1.4 created 1961]
 
 
EC 2.1.1.5     
Accepted name: betaine—homocysteine S-methyltransferase
Reaction: betaine + L-homocysteine = dimethylglycine + L-methionine
Glossary: betaine = glycine betaine = N,N,N-trimethylglycine = N,N,N-trimethylammonioacetate
Other name(s): betaine-homocysteine methyltransferase; betaine-homocysteine transmethylase
Systematic name: trimethylammonioacetate:L-homocysteine S-methyltransferase
References:
1.  Klee, W.A., Richards, H.H. and Cantoni, G.L. The synthesis of methionine by enzymic transmethylation. VII. Existence of two separate homocysteine methylpherases on mammalian liver. Biochim. Biophys. Acta 54 (1961) 157–164. [PMID: 14456704]
[EC 2.1.1.5 created 1961]
 
 
EC 2.1.1.6     
Accepted name: catechol O-methyltransferase
Reaction: S-adenosyl-L-methionine + a catechol = S-adenosyl-L-homocysteine + a guaiacol
Other name(s): COMT I ; COMT II; S-COMT (soluble form of catechol-O-methyltransferase); MB-COMT (membrane-bound form of catechol-O-methyltransferase); catechol methyltransferase; catecholamine O-methyltransferase
Systematic name: S-adenosyl-L-methionine:catechol O-methyltransferase
Comments: The mammalian enzyme acts more rapidly on catecholamines such as adrenaline or noradrenaline than on catechols.
References:
1.  Axelrod, J. and Tomchick, R. Enzymatic O-methylation of epinephrine and other catechols. J. Biol. Chem. 233 (1958) 702–705. [PMID: 13575440]
2.  Gulliver, P.A. and Tipton, K.F. The purification and properties of pig brain catechol-O-methyltransferase. J. Neurochem. 32 (1979) 1525–1529. [PMID: 438821]
3.  Huh, M.M.O. and Friedhof, A.J. Multiple molecular forms of catechol-O-methyltransferase. Evidence for two distinct forms, and their purification and physical characterization. J. Biol. Chem. 254 (1979) 299–308. [PMID: 762061]
[EC 2.1.1.6 created 1965]
 
 
EC 2.1.1.7     
Accepted name: nicotinate N-methyltransferase
Reaction: S-adenosyl-L-methionine + nicotinate = S-adenosyl-L-homocysteine + N-methylnicotinate
Other name(s): furanocoumarin 8-methyltransferase; furanocoumarin 8-O-methyltransferase
Systematic name: S-adenosyl-L-methionine:nicotinate N-methyltransferase
References:
1.  Joshi, J.G. and Handler, P. Biosynthesis of trigonelline. J. Biol. Chem. 235 (1960) 2981–2983. [PMID: 13790768]
[EC 2.1.1.7 created 1965]
 
 
EC 2.1.1.8     
Accepted name: histamine N-methyltransferase
Reaction: S-adenosyl-L-methionine + histamine = S-adenosyl-L-homocysteine + Nτ-methylhistamine
Other name(s): histamine 1-methyltransferase; histamine methyltransferase; histamine-methylating enzyme; imidazolemethyltransferase; S-adenosylmethionine-histamine N-methyltransferase
Systematic name: S-adenosyl-L-methionine:histamine N-tele-methyltransferase
References:
1.  Brown, D.D., Tomchick, R. and Axelrod, J. The distribution and properties of a histamine-methylating enzyme. J. Biol. Chem. 234 (1959) 2948–2950. [PMID: 13804910]
[EC 2.1.1.8 created 1965]
 
 
EC 2.1.1.9     
Accepted name: thiol S-methyltransferase
Reaction: S-adenosyl-L-methionine + a thiol = S-adenosyl-L-homocysteine + a methyl thioether
Other name(s): S-methyltransferase; thiol methyltransferase; TMT
Systematic name: S-adenosyl-L-methionine:thiol S-methyltransferase
Comments: H2S and a variety of alkyl, aryl and heterocyclic thiols and hydroxy thiols can act as acceptors.
References:
1.  Borchardt, R.T. and Cheng, C.F. Purification and characterization of rat liver microsomal thiol methyltransferase. Biochim. Biophys. Acta 522 (1978) 340–353. [PMID: 623768]
2.  Bremer, J. and Greenberg, D.M. Enzymic methylation of foreign sulfhydryl compounds. Biochim. Biophys. Acta 46 (1961) 217–224.
3.  Weisiger, R.A. and Jakoby, W.B. Thiol S-methyltransferase from rat liver. Arch. Biochem. Biophys. 196 (1979) 631–637. [PMID: 485170]
[EC 2.1.1.9 created 1965]
 
 
EC 2.1.1.10     
Accepted name: homocysteine S-methyltransferase
Reaction: S-methyl-L-methionine + L-homocysteine = 2 L-methionine
Other name(s): S-adenosylmethionine homocysteine transmethylase; S-methylmethionine homocysteine transmethylase; adenosylmethionine transmethylase; methylmethionine:homocysteine methyltransferase; adenosylmethionine:homocysteine methyltransferase; homocysteine methylase; homocysteine methyltransferase; homocysteine transmethylase; L-homocysteine S-methyltransferase; S-adenosyl-L-methionine:L-homocysteine methyltransferase; S-adenosylmethionine-homocysteine transmethylase; S-adenosylmethionine:homocysteine methyltransferase
Systematic name: S-methyl-L-methionine:L-homocysteine S-methyltransferase
Comments: The enzyme uses S-adenosyl-L-methionine as methyl donor less actively than S-methyl-L-methionine.
References:
1.  Balish, E. and Shapiro, S.K. Methionine biosynthesis in Escherichia coli: induction and repression of methylmethionine (or adenosylmethionine):homocysteine methyltransferase. Arch. Biochem. Biophys. 119 (1967) 62–68. [PMID: 4861151]
2.  Shapiro, S.K. Adenosylmethionine-homocysteine transmethylase. Biochim. Biophys. Acta 29 (1958) 405–409. [PMID: 13572358]
3.  Shapiro, S.K. and Yphantis, D.A. Assay of S-methylmethionine and S-adenosylmethionine homocysteine transmethylases. Biochim. Biophys. Acta 36 (1959) 241–244. [PMID: 14445542]
4.  Mudd, S.H. and Datko, A.H. The S-Methylmethionine Cycle in Lemna paucicostata. Plant Physiol. 93 (1990) 623–630. [PMID: 16667513]
5.  Ranocha, P., McNeil, S.D., Ziemak, M.J., Li, C., Tarczynski, M.C. and Hanson, A.D. The S-methylmethionine cycle in angiosperms: ubiquity, antiquity and activity. Plant J. 25 (2001) 575–584. [PMID: 11309147]
6.  Ranocha, P., Bourgis, F., Ziemak, M.J., Rhodes, D., Gage, D.A. and Hanson, A.D. Characterization and functional expression of cDNAs encoding methionine-sensitive and -insensitive homocysteine S-methyltransferases from Arabidopsis. J. Biol. Chem. 275 (2000) 15962–15968. [PMID: 10747987]
7.  Grue-Sørensen, G., Kelstrup, E., Kjær, A. and Madsen, J.Ø. Diastereospecific, enzymically catalysed transmethylation from S-methyl-L-methionine to L-homocysteine, a naturally occurring process. J. Chem. Soc. Perkin Trans. 1 (1984) 1091–1097.
[EC 2.1.1.10 created 1965, modified 2010]
 
 
EC 2.1.1.11     
Accepted name: magnesium protoporphyrin IX methyltransferase
Reaction: S-adenosyl-L-methionine + magnesium protoporphyrin IX = S-adenosyl-L-homocysteine + magnesium protoporphyrin IX 13-methyl ester
Systematic name: S-adenosyl-L-methionine:magnesium-protoporphyrin-IX O-methyltransferase
References:
1.  Gibson, K.D., Neuberger, A. and Tait, G.H. Studies on the biosynthesis of porphyrin and bacteriochlorophyll by Rhodopseudomonas spheroides. 4. S-Adenosylmethioninemagnesium protoporphyrin methyltransferase. Biochem. J. 88 (1963) 325–334. [PMID: 14063871]
2.  Shepherd, M., Reid, J.D. and Hunter, C.N. Purification and kinetic characterisation of the magnesium protoporphyrin IX methyltransferase from Synechocystis PCC6803. Biochem. J. 371 (2003) 351–360. [PMID: 12489983]
3.  Bollivar, D.W., Jiang, Z.Y., Bauer, C.E. and Beale, S.I. Heterologous expression of the bchM gene product from Rhodobacter capsulatus and demonstration that it encodes S-adenosyl-L-methionine:Mg-protoporphyrin IX methyltransferase. J. Bacteriol. 176 (1994) 5290–5296. [PMID: 8071204]
4.  Gibson, L.C. and Hunter, C.N. The bacteriochlorophyll biosynthesis gene, bchM, of Rhodobacter sphaeroides encodes S-adenosyl-L-methionine: Mg protoporphyrin IX methyltransferase. FEBS Lett. 352 (1994) 127–130. [PMID: 7925960]
5.  Ebbon, J.G. and Tait, G.H. Studies on S-adenosylmethionine-magnesium protoporphyrin methyltransferase in Euglena gracilis strain Z. Biochem. J. 111 (1969) 573–582. [PMID: 5774480]
[EC 2.1.1.11 created 1965, modified 2003]
 
 
EC 2.1.1.12     
Accepted name: methionine S-methyltransferase
Reaction: S-adenosyl-L-methionine + L-methionine = S-adenosyl-L-homocysteine + S-methyl-L-methionine
Other name(s): S-adenosyl methionine:methionine methyl transferase; methionine methyltransferase; S-adenosylmethionine transmethylase; S-adenosylmethionine-methionine methyltransferase
Systematic name: S-adenosyl-L-methionine:L-methionine S-methyltransferase
Comments: Requires Zn2+ or Mn2+
References:
1.  Karr, D. Tweto, J. and Albersheim, P. S-Adenosyl methionine: methionine methyl transferase from wheat germ. Arch. Biochem. Biophys. 121 (1967) 732–738. [PMID: 6078098]
[EC 2.1.1.12 created 1972]
 
 
EC 2.1.1.13     
Accepted name: methionine synthase
Reaction: 5-methyltetrahydrofolate + L-homocysteine = tetrahydrofolate + L-methionine
Other name(s): 5-methyltetrahydrofolate—homocysteine S-methyltransferase; 5-methyltetrahydrofolate—homocysteine transmethylase; N-methyltetrahydrofolate:L-homocysteine methyltransferase; N5-methyltetrahydrofolate methyltransferase; N5-methyltetrahydrofolate-homocysteine cobalamin methyltransferase; N5-methyltetrahydrofolic—homocysteine vitamin B12 transmethylase; B12 N5-methyltetrahydrofolate homocysteine methyltransferase; methyltetrahydrofolate—homocysteine vitamin B12 methyltransferase; tetrahydrofolate methyltransferase; tetrahydropteroylglutamate methyltransferase; tetrahydropteroylglutamic methyltransferase; vitamin B12 methyltransferase; cobalamin-dependent methionine synthase; methionine synthase (cobalamin-dependent); MetH
Systematic name: 5-methyltetrahydrofolate:L-homocysteine S-methyltransferase
Comments: Contains zinc and cobamide. The enzyme becomes inactivated occasionally during its cycle by oxidation of Co(I) to Co(II). Reactivation by reductive methylation is catalysed by the enzyme itself, with S-adenosyl-L-methionine as the methyl donor and a reducing system. For the mammalian enzyme, the reducing system involves NADPH and EC 1.16.1.8, [methionine synthase] reductase. In bacteria, the reducing agent is flavodoxin, and no further catalyst is needed (the flavodoxin is kept in the reduced state by NADPH and EC 1.18.1.2, ferredoxin—NADP+ reductase). Acts on the monoglutamate as well as the triglutamate folate, in contrast with EC 2.1.1.14, 5-methyltetrahydropteroyltriglutamate—homocysteine S-methyltransferase, which acts only on the triglutamate.
References:
1.  Burton, E.G. and Sakami, W. The formation of methionine from the monoglutamate form of methyltetrahydrofolate by higher plants. Biochem. Biophys. Res. Commun. 36 (1969) 228–234. [PMID: 5799642]
2.  Foster, M.A., Dilworth, M.J. and Woods, D.D. Cobalamin and the synthesis of methionine by Escherichia coli. Nature 201 (1964) 39–42. [PMID: 14085561]
3.  Guest, J.R., Friedman, S., Foster, M.A., Tejerina, G. and Woods, D.D. Transfer of the methyl group from N5-methyltetrahydrofolates to homocysteine in Escherichia coli. Biochem. J. 92 (1964) 497–504. [PMID: 5319972]
4.  Loughlin, R.E., Elford, H.L. and Buchanan, J.M. Enzymatic synthesis of the methyl group of methionine. VII. Isolation of a cobalamin-containing transmethylase (5-methyltetrahydro-folate-homocysteine) from mammalian liver. J. Biol. Chem. 239 (1964) 2888–2895. [PMID: 14216440]
5.  Taylor, R.T. Escherichia coli B N 5 -methyltetrahydrofolate-homocysteine cobalamin methyltransferase: gel-filtration behavior of apoenzyme and holoenzymes. Biochim. Biophys. Acta 242 (1971) 355–364. [PMID: 4946148]
6.  Jarrett, J.T., Huang, S. and Matthews, R.G. Methionine synthase exists in two distinct conformations that differ in reactivity toward methyltetrahydrofolate, adenosylmethionine, and flavodoxin. Biochemistry 37 (1998) 5372–5382. [PMID: 9548919]
7.  Peariso, K., Goulding, C.W., Huang, S., Matthews, R.G. and Penner-Hahn, J.E. Characterization of the zinc binding site in methionine synthase enzymes of Escherichia coli: The role of zinc in the methylation of homocysteine. J. Am. Chem. Soc. 120 (1998) 8410–8416.
8.  Hall, D.A., Jordan-Starck, T.C., Loo, R.O., Ludwig, M.L. and Matthews, R.G. Interaction of flavodoxin with cobalamin-dependent methionine synthase. Biochemistry 39 (2000) 10711–10719. [PMID: 10978155]
9.  Bandarian, V., Pattridge, K.A., Lennon, B.W., Huddler, D.P., Matthews, R.G. and Ludwig, M.L. Domain alternation switches B12-dependent methionine synthase to the activation conformation. Nat. Struct. Biol. 9 (2002) 53–56. [PMID: 11731805]
[EC 2.1.1.13 created 1972, modified 2003]
 
 
EC 2.1.1.14     
Accepted name: 5-methyltetrahydropteroyltriglutamate—homocysteine S-methyltransferase
Reaction: 5-methyltetrahydropteroyltri-L-glutamate + L-homocysteine = tetrahydropteroyltri-L-glutamate + L-methionine
Other name(s): tetrahydropteroyltriglutamate methyltransferase; homocysteine methylase; methyltransferase, tetrahydropteroylglutamate-homocysteine transmethylase; methyltetrahydropteroylpolyglutamate:homocysteine methyltransferase; cobalamin-independent methionine synthase; methionine synthase (cobalamin-independent); MetE
Systematic name: 5-methyltetrahydropteroyltri-L-glutamate:L-homocysteine S-methyltransferase
Comments: Requires phosphate and contains zinc. The enzyme from Escherichia coli also requires a reducing system. Unlike EC 2.1.1.13, methionine synthase, this enzyme does not contain cobalamin.
References:
1.  Guest, J.R., Friedman, S., Foster, M.A., Tejerina, G. and Woods, D.D. Transfer of the methyl group from N5-methyltetrahydrofolates to homocysteine in Escherichia coli. Biochem. J. 92 (1964) 497–504. [PMID: 5319972]
2.  Whitfield, C.D., Steers, E.J., Jr. and Weissbach, H. Purification and properties of 5-methyltetrahydropteroyltriglutamate-homocysteine transmethylase. J. Biol. Chem. 245 (1970) 390–401. [PMID: 4904482]
3.  Eichel, J., Gonzalez, J.C., Hotze, M., Matthews, R.G. and Schroder, J. Vitamin B12-independent methionine synthase from a higher-plant (Catharanthus roseus) - molecular characterization, regulation, heterologous expression, and enzyme properties. Eur. J. Biochem. 230 (1995) 1053–1058. [PMID: 7601135]
4.  Gonzalez, J.C., Peariso, K., PennerHahn, J.E. and Matthews, R.G. Cobalamin-independent methionine synthase from Escherichia coli: A zinc metalloenzyme. Biochemistry 35 (1996) 12228–12234. [PMID: 8823155]
5.  Peariso, K., Goulding, C.W., Huang, S., Matthews, R.G. and Penner-Hahn, J.E. Characterization of the zinc binding site in methionine synthase enzymes of Escherichia coli: The role of zinc in the methylation of homocysteine. J. Am. Chem. Soc. 120 (1998) 8410–8416.
[EC 2.1.1.14 created 1972, modified 2003]
 
 
EC 2.1.1.15     
Accepted name: fatty-acid O-methyltransferase
Reaction: S-adenosyl-L-methionine + a fatty acid = S-adenosyl-L-homocysteine + a fatty acid methyl ester
Other name(s): fatty acid methyltransferase; fatty acid O-methyltransferase
Systematic name: S-adenosyl-L-methionine:fatty-acid O-methyltransferase
Comments: Oleic acid is the most effective fatty acid acceptor.
References:
1.  Akamatsu, Y. and Law, J.H. The enzymatic synthesis of fatty acid methyl esters by carboxyl group alkylation. J. Biol. Chem. 245 (1970) 709–713. [PMID: 4984625]
[EC 2.1.1.15 created 1972]
 
 
EC 2.1.1.16     
Accepted name: methylene-fatty-acyl-phospholipid synthase
Reaction: S-adenosyl-L-methionine + phospholipid olefinic fatty acid = S-adenosyl-L-homocysteine + phospholipid methylene fatty acid
Other name(s): unsaturated-phospholipid methyltransferase
Systematic name: S-adenosyl-L-methionine:unsaturated-phospholipid methyltransferase (methenylating)
Comments: The enzyme transfers a methyl group to the 10-position of a Δ-olefinic acyl chain in phosphatidylglycerol or phosphatidylinositol or, more slowly, phosphatidylethanolamine; subsequent proton transfer produces a 10-methylene group (cf. EC 2.1.1.79 cyclopropane-fatty-acyl-phospholipid synthase).
References:
1.  Akamatsu, Y. and Law, J.H. Enzymatic alkylenation of phospholipid fatty acid chains by extracts of Mycobacterium phlei. J. Biol. Chem. 245 (1970) 701–708. [PMID: 4313604]
[EC 2.1.1.16 created 1972, modified 1986]
 
 
EC 2.1.1.17     
Accepted name: phosphatidylethanolamine N-methyltransferase
Reaction: S-adenosyl-L-methionine + phosphatidylethanolamine = S-adenosyl-L-homocysteine + phosphatidyl-N-methylethanolamine
Other name(s): PEMT; LMTase; lipid methyl transferase; phosphatidylethanolamine methyltransferase; phosphatidylethanolamine-N-methylase; phosphatidylethanolamine-S-adenosylmethionine methyltransferase
Systematic name: S-adenosyl-L-methionine:phosphatidylethanolamine N-methyltransferase
References:
1.  Hirata, F., Viveros, O.H., Diliberto, E.J., Jr. and Axelrod, J. Identification and properties of two methyltransferases in conversion of phosphatidylethanolamine to phosphatidylcholine. Proc. Natl. Acad. Sci. USA 75 (1978) 1718–1721. [PMID: 25437]
2.  Morgan, T.E. Isolation and characterization of lipid N-methyltransferase from dog lung. Biochim. Biophys. Acta 178 (1969) 21–34. [PMID: 5773456]
3.  Schneider, W.J. and Vance, D.E. Conversion of phosphatidylethanolamine to phosphatidylcholine in rat liver. Partial purification and characterization of the enzymatic activities. J. Biol. Chem. 254 (1979) 3886–3891. [PMID: 438165]
[EC 2.1.1.17 created 1972]
 
 
EC 2.1.1.18     
Accepted name: polysaccharide O-methyltransferase
Reaction: S-adenosyl-L-methionine + a (1→4)-α-D-glucooligosaccharide = S-adenosyl-L-homocysteine + an oligosaccharide containing 6-methyl-D-glucose units
Other name(s): polysaccharide methyltransferase; acylpolysacharide 6-methyltransferase; S-adenosyl-L-methionine:1,4-α-D-glucan 6-O-methyltransferase
Systematic name: S-adenosyl-L-methionine:(1→4)-α-D-glucan 6-O-methyltransferase
References:
1.  Ferguson, J.A. and Ballou, C.E. Biosynthesis of a mycobacterial lipopolysaccharide. Properties of the polysaccharide methyltransferase. J. Biol. Chem. 245 (1970) 4213–4223. [PMID: 5503262]
[EC 2.1.1.18 created 1972]
 
 
EC 2.1.1.19     
Accepted name: trimethylsulfonium—tetrahydrofolate N-methyltransferase
Reaction: trimethylsulfonium + tetrahydrofolate = dimethylsulfide + 5-methyltetrahydrofolate
Other name(s): trimethylsulfonium-tetrahydrofolate methyltransferase
Systematic name: trimethylsulfonium:tetrahydrofolate N-methyltransferase
References:
1.  Wagner, C., Lusty, S.M., Jr., Kung, H.-F. and Rodgers, N.L. Preparation and properties of trimethylsulfonium-tetrahydrofolate methyltransferase. J. Biol. Chem. 242 (1967) 1287–1293. [PMID: 6023571]
[EC 2.1.1.19 created 1972]
 
 
EC 2.1.1.20     
Accepted name: glycine N-methyltransferase
Reaction: S-adenosyl-L-methionine + glycine = S-adenosyl-L-homocysteine + sarcosine
Glossary: sarcosine = N-methylglycine
Other name(s): glycine methyltransferase; S-adenosyl-L-methionine:glycine methyltransferase; GNMT
Systematic name: S-adenosyl-L-methionine:glycine N-methyltransferase
Comments: This enzyme is thought to play an important role in the regulation of methyl group metabolism in the liver and pancreas by regulating the ratio between S-adenosyl-L-methionine and S-adenosyl-L-homocysteine. It is inhibited by 5-methyltetrahydrofolate pentaglutamate [4]. Sarcosine, which has no physiological role, is converted back into glycine by the action of EC 1.5.8.3, sarcosine dehydrogenase.
References:
1.  Blumenstein, J. and Williams, G.R. Glycine methyltransferase. Can. J. Biochem. Physiol. 41 (1963) 201–210. [PMID: 13971907]
2.  Ogawa, H., Gomi, T., Takusagawa, F. and Fujioka, M. Structure, function and physiological role of glycine N-methyltransferase. Int. J. Biochem. Cell Biol. 30 (1998) 13–26. [PMID: 9597750]
3.  Yeo, E.J., Briggs, W.T. and Wagner, C. Inhibition of glycine N-methyltransferase by 5-methyltetrahydrofolate pentaglutamate. J. Biol. Chem. 274 (1999) 37559–37564. [PMID: 10608809]
4.  Martinov, M.V., Vitvitsky, V.M., Mosharov, E.V., Banerjee, R. and Ataullakhanov, F.I. A substrate switch: a new mode of regulation in the methionine metabolic pathway. J. Theor. Biol. 204 (2000) 521–532. [PMID: 10833353]
5.  Takata, Y., Huang, Y., Komoto, J., Yamada, T., Konishi, K., Ogawa, H., Gomi, T., Fujioka, M. and Takusagawa, F. Catalytic mechanism of glycine N-methyltransferase. Biochemistry 42 (2003) 8394–8402. [PMID: 12859184]
6.  Pakhomova, S., Luka, Z., Grohmann, S., Wagner, C. and Newcomer, M.E. Glycine N-methyltransferases: a comparison of the crystal structures and kinetic properties of recombinant human, mouse and rat enzymes. Proteins 57 (2004) 331–337. [PMID: 15340920]
[EC 2.1.1.20 created 1972, modified 2005]
 
 
EC 2.1.1.21     
Accepted name: methylamine—glutamate N-methyltransferase
Reaction: methylamine + L-glutamate = NH3 + N-methyl-L-glutamate
Other name(s): N-methylglutamate synthase; methylamine-glutamate methyltransferase
Systematic name: methylamine:L-glutamate N-methyltransferase
References:
1.  Shaw, W.V., Tsai, L. and Stadtman, E.R. The enzymatic synthesis of N-methylglutamic acid. J. Biol. Chem. 241 (1966) 935–945. [PMID: 5905132]
[EC 2.1.1.21 created 1972]
 
 
EC 2.1.1.22     
Accepted name: carnosine N-methyltransferase
Reaction: S-adenosyl-L-methionine + carnosine = S-adenosyl-L-homocysteine + anserine
Systematic name: S-adenosyl-L-methionine:carnosine N-methyltransferase
References:
1.  McManus, I.R. Enzymatic synthesis of anserine in skeletal muscle by N-methylation of carnosine. J. Biol. Chem. 237 (1962) 1207–1211.
[EC 2.1.1.22 created 1972]
 
 
EC 2.1.1.23      
Deleted entry:  protein-arginine N-methyltransferase. Now listed as EC 2.1.1.124 [cytochrome c]-arginine N-methyltransferase, EC 2.1.1.125 histone-arginine N-methyltransferase and EC 2.1.1.126 [myelin basic protein]-arginine N-methyltransferase
[EC 2.1.1.23 created 1972, modified 1976, modified 1983, deleted 1999]
 
 
EC 2.1.1.24      
Deleted entry:  protein-γ-glutamate O-methyltransferase. Now listed as EC 2.1.1.77 protein-L-isoaspartate(D-aspartate) O-methyltransferase, EC 2.1.1.80 protein-glutamate O-methyltransferase and EC 2.1.1.100 protein-S-isoprenylcysteine O-methyltransferase
[EC 2.1.1.24 created 1972, modified 1983, modified 1989, deleted 1992]
 
 
EC 2.1.1.25     
Accepted name: phenol O-methyltransferase
Reaction: S-adenosyl-L-methionine + phenol = S-adenosyl-L-homocysteine + anisole
Other name(s): PMT
Systematic name: S-adenosyl-L-methionine:phenol O-methyltransferase
Comments: Acts on a wide variety of simple alkyl-, methoxy- and halo-phenols.
References:
1.  Axelrod, J. and Daly, J. Phenol-O-methyltransferase. Biochim. Biophys. Acta 159 (1968) 472–478. [PMID: 5657870]
[EC 2.1.1.25 created 1972]
 
 
EC 2.1.1.26     
Accepted name: iodophenol O-methyltransferase
Reaction: S-adenosyl-L-methionine + 2-iodophenol = S-adenosyl-L-homocysteine + 2-iodophenol methyl ether
Systematic name: S-adenosyl-L-methionine:2-iodophenol O-methyltransferase
References:
1.  Tomita, K., Cha, C.-J. and Lardy, H.A. Enzymic O-methylation of iodinated phenols and thyroid hormones. J. Biol. Chem. 239 (1964) 1202–1207. [PMID: 14165927]
[EC 2.1.1.26 created 1972]
 
 
EC 2.1.1.27     
Accepted name: tyramine N-methyltransferase
Reaction: S-adenosyl-L-methionine + tyramine = S-adenosyl-L-homocysteine + N-methyltyramine
Other name(s): DIB O-methyltransferase (3,5-diiodo-4-hydroxy-benzoic acid); S-adenosyl-methionine:tyramine N-methyltransferase; tyramine methylpherase
Systematic name: S-adenosyl-L-methionine:tyramine N-methyltransferase
Comments: Has some activity on phenylethylamine analogues.
References:
1.  Mann, J.D. and Mudd, S.H. Alkaloids and plant metabolism. IV. The tyramine methylpherase of barley roots. J. Biol. Chem. 238 (1963) 381–385.
[EC 2.1.1.27 created 1972]
 
 
EC 2.1.1.28     
Accepted name: phenylethanolamine N-methyltransferase
Reaction: S-adenosyl-L-methionine + phenylethanolamine = S-adenosyl-L-homocysteine + N-methylphenylethanolamine
Other name(s): noradrenaline N-methyltransferase; noradrenalin N-methyltransferase; norepinephrine methyltransferase; norepinephrine N-methyltransferase; phenethanolamine methyltransferase; phenethanolamine N-methyltransferase
Systematic name: S-adenosyl-L-methionine:phenylethanolamine N-methyltransferase
Comments: Acts on various phenylethanolamines; converts noradrenaline into adrenaline.
References:
1.  Axelrod, J. Purification and properties of phenylethanolamine-N-methyl transferase. J. Biol. Chem. 237 (1962) 1657–1660. [PMID: 13863458]
2.  Connett, R.J. and Kirschner, N. Purification and properties of bovine phenylethanolamine N-methyltransferase. J. Biol. Chem. 245 (1970) 329–334. [PMID: 5412063]
[EC 2.1.1.28 created 1972]
 
 
EC 2.1.1.29      
Transferred entry: tRNA (cytosine-5-)-methyltransferase. Now covered by EC 2.1.1.202 [multisite-specific tRNA:(cytosine-C5)-methyltransferase], EC 2.1.1.203 [tRNA (cytosine34-C5)-methyltransferase] and EC 2.1.1.204 [RNA (cytosine38-C5)-methyltransferase].
[EC 2.1.1.29 created 1972, deleted 2011]
 
 
EC 2.1.1.30      
Deleted entry: tRNA (purine-2- or -6-)-methyltransferase. Reactions previously described are due to EC 2.1.1.32 tRNA (guanine-N2-)-methyltransferase
[EC 2.1.1.30 created 1972, deleted 1981]
 
 
EC 2.1.1.31      
Transferred entry: tRNA (guanine-N1-)-methyltransferase. Now covered by EC 2.1.1.221 (tRNA (guanine9-N1)-methyltransferase) and EC 2.1.1.228 (tRNA (guanine37-N1)-methyltransferase).
[EC 2.1.1.31 created 1972, deleted 2011]
 
 
EC 2.1.1.32      
Transferred entry: tRNA (guanine-N2-)-methyltransferase. Now covered by EC 2.1.1.213 [tRNA (guanine10-N2)-dimethyltransferase], EC 2.1.1.214 [tRNA (guanine10-N2)-monomethyltransferase], EC 2.1.1.215 [tRNA (guanine26-N2/guanine27-N2)-dimethyltransferase] and EC 2.1.1.216 [tRNA (guanine26-N2)-dimethyltransferase]
[EC 2.1.1.32 created 1972, deleted 2011]
 
 
EC 2.1.1.33     
Accepted name: tRNA (guanine46-N7)-methyltransferase
Reaction: S-adenosyl-L-methionine + guanine46 in tRNA = S-adenosyl-L-homocysteine + N7-methylguanine46 in tRNA
Other name(s): Trm8/Trm82; TrmB; tRNA (m7G46) methyltransferase; transfer ribonucleate guanine 7-methyltransferase; 7-methylguanine transfer ribonucleate methylase; tRNA guanine 7-methyltransferase; N7-methylguanine methylase; S-adenosyl-L-methionine:tRNA (guanine-7-N-)-methyltransferase
Systematic name: S-adenosyl-L-methionine:tRNA (guanine-N7)-methyltransferase
Comments: The enzyme specifically methylates guanine46 at N7 in tRNA.
References:
1.  Aschhoff, H.J., Elten, H., Arnold, H.H., Mahal, G., Kersten, W. and Kersten, H. 7-Methylguanine specific tRNA-methyltransferase from Escherichia coli. Nucleic Acids Res. 3 (1976) 3109–3122. [PMID: 794833]
2.  Zegers, I., Gigot, D., van Vliet, F., Tricot, C., Aymerich, S., Bujnicki, J.M., Kosinski, J. and Droogmans, L. Crystal structure of Bacillus subtilis TrmB, the tRNA (m7G46) methyltransferase. Nucleic Acids Res. 34 (2006) 1925–1934. [PMID: 16600901]
3.  Purta, E., van Vliet, F., Tricot, C., De Bie, L.G., Feder, M., Skowronek, K., Droogmans, L. and Bujnicki, J.M. Sequence-structure-function relationships of a tRNA (m7G46) methyltransferase studied by homology modeling and site-directed mutagenesis. Proteins 59 (2005) 482–488. [PMID: 15789416]
4.  Liu, Q., Gao, Y., Yang, W., Zhou, H., Gao, Y., Zhang, X., Teng, M. and Niu, L. Crystallization and preliminary crystallographic analysis of tRNA (m7G46) methyltransferase from Escherichia coli. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 64 (2008) 743–745. [PMID: 18678947]
5.  Alexandrov, A., Martzen, M.R. and Phizicky, E.M. Two proteins that form a complex are required for 7-methylguanosine modification of yeast tRNA. RNA 8 (2002) 1253–1266. [PMID: 12403464]
[EC 2.1.1.33 created 1972, modified 2011]
 
 
EC 2.1.1.34     
Accepted name: tRNA (guanosine18-2′-O)-methyltransferase
Reaction: S-adenosyl-L-methionine + guanosine18 in tRNA = S-adenosyl-L-homocysteine + 2′-O-methylguanosine18 in tRNA
Other name(s): tRNA (Gm18) 2′-O-methyltransferase; tRNA (Gm18) methyltransferase; TrmH; SpoU
Systematic name: S-adenosyl-L-methionine:tRNA (guanosine18-2′-O)-methyltransferase
Comments: The enzyme catalyses the methylation of guanosine18 in tRNA.
References:
1.  Gefter, M.L. The in vitro synthesis of 2′-O-methylguanosine and 2-methylthio 6N (γ,gamma-dimethylallyl) adenosine in transfer RNA of Escherichia coli. Biochem. Biophys. Res. Commun. 36 (1969) 435–441. [PMID: 4898378]
2.  Kumagai, I., Watanabe, K. and Oshima, T. Thermally induced biosynthesis of 2′-O-methylguanosine in tRNA from an extreme thermophile, Thermus thermophilus HB27. Proc. Natl. Acad. Sci. USA 77 (1980) 1922–1926. [PMID: 6990416]
3.  Hori, H., Yamazaki, N., Matsumoto, T., Watanabe, Y., Ueda, T., Nishikawa, K., Kumagai, I. and Watanabe, K. Substrate recognition of tRNA (guanosine-2′-)-methyltransferase from Thermus thermophilus HB27. J. Biol. Chem. 273 (1998) 25721–25727. [PMID: 9748240]
4.  Pleshe, E., Truesdell, J. and Batey, R.T. Structure of a class II TrmH tRNA-modifying enzyme from Aquifex aeolicus. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 61 (2005) 722–728. [PMID: 16511140]
5.  Ochi, A., Makabe, K., Kuwajima, K. and Hori, H. Flexible recognition of the tRNA G18 methylation target site by TrmH methyltransferase through first binding and induced fit processes. J. Biol. Chem. 285 (2010) 9018–9029. [PMID: 20053984]
[EC 2.1.1.34 created 1972, modified 2005, modified 2011]
 
 
EC 2.1.1.35     
Accepted name: tRNA (uracil54-C5)-methyltransferase
Reaction: S-adenosyl-L-methionine + uracil54 in tRNA = S-adenosyl-L-homocysteine + 5-methyluracil54 in tRNA
Other name(s): transfer RNA uracil54 5-methyltransferase; transfer RNA uracil54 methylase; tRNA uracil54 5-methyltransferase; m5U54-methyltransferase; tRNA:m5U54-methyltransferase; RUMT; TrmA; 5-methyluridine54 tRNA methyltransferase; tRNA(uracil-54,C5)-methyltransferase; Trm2; tRNA(m5U54)methyltransferase
Systematic name: S-adenosyl-L-methionine:tRNA (uracil54-C5)-methyltransferase
Comments: Unlike this enzyme, EC 2.1.1.74 (methylenetetrahydrofolate—tRNA-(uracil54-C5)-methyltransferase (FADH2-oxidizing)), uses 5,10-methylenetetrahydrofolate and FADH2 to supply the atoms for methylation of U54 [4].
References:
1.  Björk, G.R. and Svensson, I. Studies on microbial RNA. Fractionation of tRNA methylases from Saccharomyces cerevisiae. Eur. J. Biochem. 9 (1969) 207–215. [PMID: 4896260]
2.  Greenberg, R. and Dudock, B. Isolation and characterization of m5U-methyltransferase from Escherichia coli. J. Biol. Chem. 255 (1980) 8296–8302. [PMID: 6997293]
3.  Hurwitz, J., Gold, M. and Anders, M. The enzymatic methylation of ribonucleic acid and deoxyribonucleic acid. 3. Purification of soluble ribonucleic acid-methylating enzymes. J. Biol. Chem. 239 (1964) 3462–3473. [PMID: 14245404]
4.  Delk, A.S., Nagle, D.P., Jr. and Rabinowitz, J.C. Methylenetetrahydrofolate-dependent biosynthesis of ribothymidine in transfer RNA of Streptococcus faecalis. Evidence for reduction of the 1-carbon unit by FADH2. J. Biol. Chem. 255 (1980) 4387–4390. [PMID: 6768721]
5.  Kealey, J.T., Gu, X. and Santi, D.V. Enzymatic mechanism of tRNA (m5U54)methyltransferase. Biochimie 76 (1994) 1133–1142. [PMID: 7748948]
6.  Gu, X., Ivanetich, K.M. and Santi, D.V. Recognition of the T-arm of tRNA by tRNA (m5U54)-methyltransferase is not sequence specific. Biochemistry 35 (1996) 11652–11659. [PMID: 8794745]
7.  Becker, H.F., Motorin, Y., Sissler, M., Florentz, C. and Grosjean, H. Major identity determinants for enzymatic formation of ribothymidine and pseudouridine in the TΨ-loop of yeast tRNAs. J. Mol. Biol. 274 (1997) 505–518. [PMID: 9417931]
8.  Walbott, H., Leulliot, N., Grosjean, H. and Golinelli-Pimpaneau, B. The crystal structure of Pyrococcus abyssi tRNA (uracil-54, C5)-methyltransferase provides insights into its tRNA specificity. Nucleic Acids Res. 36 (2008) 4929–4940. [PMID: 18653523]
[EC 2.1.1.35 created 1972, modified 2011]
 
 
EC 2.1.1.36      
Transferred entry: tRNA (adenine-N1-)-methyltransferase. Now covered by EC 2.1.1.217 (tRNA (adenine22-N1)-methyltransferase), EC 2.1.1.218 (tRNA (adenine9-N1)-methyltransferase), EC 2.1.1.219 (tRNA (adenine57-N1/adenine58-N1)-methyltransferase), EC 2.1.1.220 (tRNA (adenine58-N1)-methyltransferase).
[EC 2.1.1.36 created 1972, deleted 2011]
 
 
EC 2.1.1.37     
Accepted name: DNA (cytosine-5-)-methyltransferase
Reaction: S-adenosyl-L-methionine + DNA containing cytosine = S-adenosyl-L-homocysteine + DNA containing 5-methylcytosine
Other name(s): EcoRI methylase; DNA 5-cytosine methylase; DNA cytosine C5 methylase; DNA cytosine methylase; DNA methylase (ambiguous); DNA methyltransferase (ambiguous); DNA transmethylase (ambiguous); DNA-cytosine 5-methylase; DNA-cytosine methyltransferase; HpaII methylase; HpaII′ methylase; M.BsuRIa; M.BsuRIb; Type II DNA methylase; cytosine 5-methyltransferase; cytosine DNA methylase; cytosine DNA methyltransferase; cytosine-specific DNA methyltransferase; deoxyribonucleate methylase (ambiguous); deoxyribonucleate methyltransferase (ambiguous); deoxyribonucleic (cytosine-5-)-methyltransferase; deoxyribonucleic acid (cytosine-5-)-methyltransferase; deoxyribonucleic acid methylase (ambiguous); deoxyribonucleic acid methyltransferase (ambiguous); deoxyribonucleic acid modification methylase (ambiguous); deoxyribonucleic methylase (ambiguous); methylphosphotriester-DNA methyltransferase (ambiguous); modification methylase (ambiguous); restriction-modification system (ambiguous); site-specific DNA-methyltransferase (cytosine-specific); DNA-(cytosine C5)-methylase
Systematic name: S-adenosyl-L-methionine:DNA (cytosine-5-)-methyltransferase
References:
1.  Gold, M. and Hurwitz, J. The enzymatic methylation of ribonucleic acid and deoxyribonucleic acid. V. Purification and properties of the deoxyribonucleic acid-methylating activity of Escherichia coli. J. Biol. Chem. 239 (1964) 3858. [PMID: 14257620]
2.  Kalousek, F. and Morris, N.R. The purification and properties of deoxyribonucleic acid methylase from rat spleen. J. Biol. Chem. 244 (1969) 1157–1163. [PMID: 4975067]
3.  Roy, P.H. and Weissbach, A. DNA methylase from HeLa cell nuclei. Nucleic Acids Res. 2 (1975) 1669–1684. [PMID: 1187340]
4.  Simon, D., Grunert, F., Acken, U.Y., Döring, H.P. and Kröger, H. DNA-methylase from regenerating rat liver: purification and characterisation. Nucleic Acids Res. 5 (1978) 2153–2167. [PMID: 673848]
5.  Sneider, T.W., Teague, W.M. and Rogachewsky, L.M. S-Adenosylmethionine: DNA-cytosine 5-methyltransferase from a Novikoff rat hepatoma cell line. Nucleic Acids Res. 2 (1975) 1685–1700. [PMID: 171625]
6.  Turnbull, J.F. and Adams, R.L.P. DNA methylase: purification from ascites cells and the effect of various DNA substrates on its activity. Nucleic Acids Res. 3 (1976) 677–695. [PMID: 131936]
7.  Kessler, C. and Manta, V. Specificity of restriction endonucleases and DNA modification methyltransferases: a review. Gene 92 (1990) 1–248. [PMID: 2172084]
8.  Roberts, R.J. Restriction enzymes and their isoschizomers. Nucleic Acids Res. 18 (1990) 2331–2365. [PMID: 2159140]
9.  Yuan, R. Structure and mechanism of multifunctional restriction endonucleases. Annu. Rev. Biochem. 50 (1981) 285–319. [PMID: 6267988]
[EC 2.1.1.37 created 1972, (EC 2.1.1.73 incorporated 2003), modified 2003]
 
 
EC 2.1.1.38     
Accepted name: O-demethylpuromycin O-methyltransferase
Reaction: S-adenosyl-L-methionine + O-demethylpuromycin = S-adenosyl-L-homocysteine + puromycin
Other name(s): O-demethylpuromycin methyltransferase
Systematic name: S-adenosyl-L-methionine:O-demethylpuromycin O-methyltransferase
Comments: Puromycin is the antibiotic derived from N6-dimethyladenosine by replacing the 3′-hydroxy group with an amino group and acylating this with 4-O-methyltyrosine.
References:
1.  Rao, M.M., Rebello, P.F. and Pogell, B.M. Biosynthesis of puromycin in Streptomyces alboniger. Enzymatic methylation of O-demethylpuromycin. J. Biol. Chem. 244 (1969) 112–118. [PMID: 5773275]
[EC 2.1.1.38 created 1972]
 
 
EC 2.1.1.39     
Accepted name: inositol 3-methyltransferase
Reaction: S-adenosyl-L-methionine + myo-inositol = S-adenosyl-L-homocysteine + 1D-3-O-methyl-myo-inositol
Other name(s): inositol L-1-methyltransferase; myo-inositol 1-methyltransferase; S-adenosylmethionine:myo-inositol 1-methyltransferase; myo-inositol 1-O-methyltransferase (name based on 1L-numbering system and not 1D-numbering); S-adenosyl-L-methionine:myo-inositol 1-O-methyltransferase
Systematic name: S-adenosyl-L-methionine:1D-myo-inositol 3-O-methyltransferase
References:
1.  Hofmann, H., Wagner, I. and Hoffmann-Ostenhof, O. Untersuchungen über die Biosynthese der Cyclite. XXIV. Über ein lösliches Enzym aus Vinca rosea, das myo-Inosit zu L-Bornesit methyliert. Hoppe-Seyler's Z. Physiol. Chem. 350 (1969) 1465–1468. [PMID: 5362621]
[EC 2.1.1.39 created 1972, modified 2002]
 
 
EC 2.1.1.40     
Accepted name: inositol 1-methyltransferase
Reaction: S-adenosyl-L-methionine + myo-inositol = S-adenosyl-L-homocysteine + 1D-1-O-methyl-myo-inositol
Other name(s): inositol D-1-methyltransferase; S-adenosylmethionine:myo-inositol 3-methyltransferase; myo-inositol 3-O-methyltransferase; inositol 3-O-methyltransferase (name based on 1L-numbering system and not 1D-numbering); S-adenosyl-L-methionine:myo-inositol 3-O-methyltransferase
Systematic name: S-adenosyl-L-methionine:1D-myo-inositol 1-O-methyltransferase
References:
1.  Wagner, I., Hofmann, H. and Hoffmann-Ostenhof, O. Untersuchungen über die Biosynthese der Cyclite. XXIII. Über ein lösliches Enzym aus Erbsenkeimlingen, das myo-Inosit zu D-Bornesit methyliert. Hoppe-Seyler's Z. Physiol. Chem. 350 (1969) 1460–1464. [PMID: 5362620]
[EC 2.1.1.40 created 1972, modified 2002]
 
 
EC 2.1.1.41     
Accepted name: sterol 24-C-methyltransferase
Reaction: S-adenosyl-L-methionine + 5α-cholesta-8,24-dien-3β-ol = S-adenosyl-L-homocysteine + 24-methylene-5α-cholest-8-en-3β-ol
Glossary: desmosterol = cholesta-5,24-dien-3β-ol
zymostrol = 5α-cholesta-8,24-dien-3β-ol
Other name(s): Δ24-methyltransferase; Δ24-sterol methyltransferase; zymosterol-24-methyltransferase; S-adenosyl-4-methionine:sterol Δ24-methyltransferase; SMT1; 24-sterol C-methyltransferase; S-adenosyl-L-methionine:Δ24(23)-sterol methyltransferase; phytosterol methyltransferase
Systematic name: S-adenosyl-L-methionine:zymosterol 24-C-methyltransferase
Comments: Requires glutathione. Acts on a range of sterols with a 24(25)-double bond in the sidechain. While zymosterol is the preferred substrate it also acts on desmosterol, 5α-cholesta-7,24-dien-3β-ol, 5α-cholesta-5,7,24-trien-3β-ol, 4α-methylzymosterol and others. S-Adenosyl-L-methionine attacks the Si-face of the 24(25) double bond and the C-24 hydrogen is transferred to C-25 on the Re face of the double bond.
References:
1.  Moore, J.T., Jr. and Gaylor, J.L. Isolation and purification of an S-adenosylmethionine: Δ24-sterol methyltransferase from yeast. J. Biol. Chem. 244 (1969) 6334–6340. [PMID: 5354959]
2.  Venkatramesh, M., Guo, D., Jia, Z. and Nes, W.D. Mechanism and structural requirements for transformations of substrates by the S-adenosyl-L-methionine:Δ24(25)-sterol methyl transferase enzyme from Saccharomyces cerevisiae. Biochim. Biophys. Acta 1299 (1996) 313–324. [PMID: 8597586]
3.  Tong, Y., McCourt, B.S., Guo, D., Mangla, A.T., Zhou, W.X., Jenkins, M.D., Zhou, W., Lopez, M. and Nes, W.D. , Stereochemical features of C-methylation on the path to Δ24(28)-methylene and Δ24(28)-ethylidene sterols: studies on the recombinant phytosterol methyl transferase from Arabidopsis thaliana. Tetrahedron Lett. 38 (1997) 6115–6118.
4.  Bouvier-Navé, P., Husselstein, T. and Benveniste, P. Two families of sterol methyltransferases are involved in the first and the second methylation steps of plant biosynthesis. Eur. J. Biochem. 256 (1998) 88–96. [PMID: 9746350]
5.  Nes, W.D., McCourt, B.S., Zhou, W., Ma, J., Marshall, J.A., Peek, L.A. and Brennan, M. Overexpression, purification, and stereochemical studies of the recombinant S-adenosyl-L-methionine:Δ24(25)- to Δ24(28)-sterol methyl transferase enzyme from Saccharomyces cerevisiae sterol methyl transferase. Arch. Biochem. Biophys. 353 (1998) 297–311. [PMID: 9606964]
[EC 2.1.1.41 created 1972, modified 2001]
 
 
EC 2.1.1.42     
Accepted name: flavone 3′-O-methyltransferase
Reaction: S-adenosyl-L-methionine + 3′-hydroxyflavone = S-adenosyl-L-homocysteine + 3′-methoxyflavone
Other name(s): o-dihydric phenol methyltransferase; luteolin methyltransferase; luteolin 3′-O-methyltransferase; o-diphenol m-O-methyltransferase; o-dihydric phenol meta-O-methyltransferase; S-adenosylmethionine:flavone/flavonol 3′-O-methyltransferase; quercetin 3′-O-methyltransferase
Systematic name: S-adenosyl-L-methionine:3′-hydroxyflavone 3′-O-methyltransferase
Comments: The enzyme prefers flavones with vicinal 3′,4′-dihydroxyl groups.
References:
1.  Ebel, J., Hahlbrock, K. and Grisebach, H. Purification and properties of an o-dihydricphenol meta-O-methyltransferase from cell suspension cultures of parsley and its relation to flavonoid biosynthesis. Biochim. Biophys. Acta 268 (1972) 313–326. [PMID: 5026305]
2.  Muzac, I., Wang, J., Anzellotti, D., Zhang, H. and Ibrahim, R.K. Functional expression of an Arabidopsis cDNA clone encoding a flavonol 3′-O-methyltransferase and characterization of the gene product. Arch. Biochem. Biophys. 375 (2000) 385–388. [PMID: 10700397]
3.  Poulton, J.E., Hahlbrock, K. and Grisebach, H. O-Methylation of flavonoid substrates by a partially purified enzyme from soybean cell suspension cultures. Arch. Biochem. Biophys. 180 (1977) 543–549. [PMID: 18099]
4.  Kim, B.G., Lee, H.J., Park, Y., Lim, Y. and Ahn, J.H. Characterization of an O-methyltransferase from soybean. Plant Physiol. Biochem. 44 (2006) 236–241. [PMID: 16777424]
5.  Lee, Y.J., Kim, B.G., Chong, Y., Lim, Y. and Ahn, J.H. Cation dependent O-methyltransferases from rice. Planta 227 (2008) 641–647. [PMID: 17943312]
[EC 2.1.1.42 created 1976, modified 2011]
 
 
EC 2.1.1.43      
Transferred entry: histone-lysine N-methyltransferase. Now described by EC 2.1.1.354, [histone H3]-lysine4 N-trimethyltransferase; EC 2.1.1.355, [histone H3]-lysine9 N-trimethyltransferase; EC 2.1.1.356, [histone H3]-lysine27 N-trimethyltransferase; EC 2.1.1.357, [histone H3]-lysine36 N-dimethyltransferase; EC 2.1.1.358, [histone H3]-dimethyl-L-lysine36 N-methyltransferase; EC 2.1.1.359, [histone H3]-lysine36 N-trimethyltransferase; EC 2.1.1.360, [histone H3]-lysine79 N-trimethyltransferase; EC 2.1.1.361, [histone H4]-lysine20 N-methyltransferase, and EC 2.1.1.362, [histone H4]-N-methyl-L-lysine20 N-methyltransferase.
[EC 2.1.1.43 created 1976, modified 1982, modified 1983, deleted 2019]
 
 
EC 2.1.1.44     
Accepted name: L-histidine Nα-methyltransferase
Reaction: 3 S-adenosyl-L-methionine + L-histidine = 3 S-adenosyl-L-homocysteine + hercynine (overall reaction)
(1a) S-adenosyl-L-methionine + L-histidine = S-adenosyl-L-homocysteine + Nα-methyl-L-histidine
(1b) S-adenosyl-L-methionine + Nα-methyl-L-histidine = S-adenosyl-L-homocysteine + Nα,Nα-dimethyl-L-histidine
(1c) S-adenosyl-L-methionine + Nα,Nα-dimethyl-L-histidine = S-adenosyl-L-homocysteine + hercynine
Glossary: hercynine = Nα,Nα,Nα-trimethyl-L-histidine
Other name(s): dimethylhistidine N-methyltransferase; dimethylhistidine methyltransferase; histidine-α-N-methyltransferase; S-adenosyl-L-methionine:α-N,α-N-dimethyl-L-histidine α-N-methyltransferase; S-adenosyl-L-methionine:Nα,Nα-dimethyl-L-histidine Nα-methyltransferase
Systematic name: S-adenosyl-L-methionine:L-histidine Nα-methyltransferase (hercynine-forming)
Comments: Part of the biosynthetic pathway of ergothioneine.
References:
1.  Ishikawa, Y. and Melville, D.B. The enzymatic α-N-methylation of histidine. J. Biol. Chem. 245 (1970) 5967–5973. [PMID: 5484456]
2.  Seebeck, F.P. In vitro reconstitution of mycobacterial ergothioneine biosynthesis. J. Am. Chem. Soc. 132 (2010) 6632–6633. [PMID: 20420449]
[EC 2.1.1.44 created 1976, modified 2013]
 
 
EC 2.1.1.45     
Accepted name: thymidylate synthase
Reaction: 5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP
Other name(s): dTMP synthase; thymidylate synthetase; methylenetetrahydrofolate:dUMP C-methyltransferase; TMP synthetase
Systematic name: 5,10-methylenetetrahydrofolate:dUMP C-methyltransferase
References:
1.  Blakley, R.L. The biosynthesis of thymidylic acid. IV. Further studies on thymidylate synthase. J. Biol. Chem. 238 (1963) 2113–2118.
2.  Lockshin, A., Moran, R.G. and Danenberg, P.V. Thymidylate synthetase purified to homogeneity from human leukemic cells. Proc. Natl. Acad. Sci. USA 76 (1979) 750–754. [PMID: 34155]
3.  Slavik, K. and Slavikova, V. Purification of thymidylate synthetase from enzyme-poor sources by affinity chromatography. Methods Enzymol. 66 (1980) 709–723. [PMID: 6990200]
4.  Wahba, A.J. and Friedkin, M. The enzymatic synthesis of thymidylate. I. Early steps in the purification of thymidylate synthetase of Escherichia coli. J. Biol. Chem. 237 (1962) 3794–3801. [PMID: 13998281]
[EC 2.1.1.45 created 1976]
 
 
EC 2.1.1.46     
Accepted name: isoflavone 4′-O-methyltransferase
Reaction: S-adenosyl-L-methionine + a 4′-hydroxyisoflavone = S-adenosyl-L-homocysteine + a 4′-methoxyisoflavone
Other name(s): 4′-hydroxyisoflavone methyltransferase; isoflavone methyltransferase; isoflavone O-methyltransferase
Systematic name: S-adenosyl-L-methionine:4′-hydroxyisoflavone 4′-O-methyltransferase
Comments: Requires Mg2+ for activity. The enzyme catalyses the methylation of daidzein and genistein. It does not methylate naringenin, apigenin, luteolin or kaempferol.
References:
1.  Wengenmayer, H., Ebel, J. and Grisebach, H. Purification and properties of a S-adenosylmethionine: isoflavone 4′-O-methyltransferase from cell suspension cultures of Cicer arietinum L. Eur. J. Biochem. 50 (1974) 135–143. [PMID: 4452353]
[EC 2.1.1.46 created 1976, modified 2011]
 
 
EC 2.1.1.47     
Accepted name: indolepyruvate C-methyltransferase
Reaction: S-adenosyl-L-methionine + (indol-3-yl)pyruvate = S-adenosyl-L-homocysteine + (R)-3-(indol-3-yl)-2-oxobutanoate
Other name(s): ind1 (gene name); indolepyruvate methyltransferase; indolepyruvate 3-methyltransferase; indolepyruvic acid methyltransferase; S-adenosyl-L-methionine:indolepyruvate C-methyltransferase
Systematic name: S-adenosyl-L-methionine:(indol-3-yl)pyruvate C3-methyltransferase
Comments: The enzyme, characterized from the bacterium Streptomyces griseus, is involved in the biosynthesis of the antibacterial drug indolmycin.
References:
1.  Hornemann, U., Speedie, M.K., Hurley, L.H. and Floss, H.G. Demonstration of a C-methylating enzyme in cell free extracts of indolmycin-producing Streptomyces griseus. Biochem. Biophys. Res. Commun. 39 (1970) 594–599. [PMID: 5490210]
2.  Hornemann, U., Hurley, L.H., Speedie, M.K. and Floss, H.G. The biosynthesis of indolmycin. J. Am. Chem. Soc. 93 (1971) 3028–3035. [PMID: 5095271]
3.  Speedie, M.K., Hornemann, U. and Floss, H.G. Isolation and characterization of tryptophan transaminase and indolepyruvate C-methyltransferase. Enzymes involved in indolmycin biosynthesis in Streptomyces griseus. J. Biol. Chem. 250 (1975) 7819–7825. [PMID: 809439]
4.  Du, Y.L., Alkhalaf, L.M. and Ryan, K.S. In vitro reconstitution of indolmycin biosynthesis reveals the molecular basis of oxazolinone assembly. Proc. Natl. Acad. Sci. USA 112 (2015) 2717–2722. [PMID: 25730866]
[EC 2.1.1.47 created 1976, modified 2016]
 
 
EC 2.1.1.48      
Transferred entry: rRNA (adenine-N6-)-methyltransferase. Now covered by EC 2.1.1.181 [23S rRNA (adenine1618-N6)-methyltransferase], EC 2.1.1.182 [16S rRNA adenine1518-N6/adenine1519-N6)-dimethyltransferase], EC 2.1.1.183 [18S rRNA (adenine1779-N6/adenine1780-N6)-dimethyltransferase] and EC 2.1.1.184 [23S rRNA (adenine2085-N6)-dimethyltransferase]
[EC 2.1.1.48 created 1976, deleted 2010]
 
 
EC 2.1.1.49     
Accepted name: amine N-methyltransferase
Reaction: S-adenosyl-L-methionine + an amine = S-adenosyl-L-homocysteine + a methylated amine
Other name(s): nicotine N-methyltransferase; tryptamine N-methyltransferase; arylamine N-methyltransferase; tryptamine methyltransferase
Systematic name: S-adenosyl-L-methionine:amine N-methyltransferase
Comments: An enzyme of very broad specificity; many primary, secondary and tertiary amines can act as acceptors, including tryptamine, aniline, nicotine and a variety of drugs and other xenobiotics.
References:
1.  Ansher, S.S. and Jakoby, W.B. Amine N-methyltransferases from rabbit liver. J. Biol. Chem. 261 (1986) 3996–4001. [PMID: 3949799]
2.  Crooks, P.A., Godin, C.S., Damani, L.A., Ansher, S.S. and Jakoby, W.B. Formation of quaternary amines by N-methylation of azaheterocycles with homogeneous amine N-methyltransferases. Biochem. Pharmacol. 37 (1988) 1673–1677. [PMID: 3377829]
[EC 2.1.1.49 created 1976, modified 1990 (EC 2.1.1.81 created 1989, incorporated 1990)]
 
 
EC 2.1.1.50     
Accepted name: loganate O-methyltransferase
Reaction: S-adenosyl-L-methionine + loganate = S-adenosyl-L-homocysteine + loganin
Other name(s): loganate methyltransferase; S-adenosyl-L-methionine:loganic acid methyltransferase
Systematic name: S-adenosyl-L-methionine:loganate 11-O-methyltransferase
Comments: Also acts on secologanate. Methylates the 11-carboxy group of the monoterpenoid loganate.
References:
1.  Madyastha, K.M., Guarnaccia, R., Baxter, C. and Coscia, C.J. S-Adenosyl-L-methionine: loganic acid methyltransferase. A carboxyl-alkylating enzyme from Vinca rosea. J. Biol. Chem. 248 (1973) 2497–2501. [PMID: 4698228]
[EC 2.1.1.50 created 1976]
 
 
EC 2.1.1.51      
Transferred entry: rRNA (guanine-N1-)-methyltransferase. Now covered by EC 2.1.1.187 [23S rRNA (guanine745-N1)-methyltransferase] and EC 2.1.1.188 [23S rRNA (guanine748-N1)-methyltransferase].
[EC 2.1.1.51 created 1976, deleted 2010]
 
 
EC 2.1.1.52      
Transferred entry: rRNA (guanine-N2-)-methyltransferase. Now covered by EC 2.1.1.171 [16S rRNA (guanine966-N2)-methyltransferase], EC 2.1.1.172 [16S rRNA (guanine1207-N2)-methyltransferase], EC 2.1.1.173 [23S rRNA (guanine2445-N2)-methyltransferase] and EC 2.1.1.174 [23S rRNA (guanine1835-N2)-methyltransferase]
[EC 2.1.1.52 created 1976, deleted 2010]
 
 
EC 2.1.1.53     
Accepted name: putrescine N-methyltransferase
Reaction: S-adenosyl-L-methionine + putrescine = S-adenosyl-L-homocysteine + N-methylputrescine
Glossary: putrescine = butane-1,4-diamine
Other name(s): putrescine methyltransferase
Systematic name: S-adenosyl-L-methionine:putrescine N-methyltransferase
References:
1.  Mizusaki, S., Tanabe, Y., Noguchi, M. and Tamaki, E. Phytochemical studies on tobacco alkaloids. XIV. The occurence and properties of putrescine N-methyltransferase in tobacco roots. Plant Cell Physiol. 12 (1971) 633–640.
[EC 2.1.1.53 created 1976]
 
 
EC 2.1.1.54     
Accepted name: deoxycytidylate C-methyltransferase
Reaction: 5,10-methylenetetrahydrofolate + dCMP = dihydrofolate + deoxy-5-methylcytidylate
Other name(s): deoxycytidylate methyltransferase; dCMP methyltransferase
Systematic name: 5,10-methylenetetrahydrofolate:dCMP C-methyltransferase
Comments: dCMP is methylated by formaldehyde in the presence of tetrahydrofolate. CMP, dCTP and CTP can act as acceptors, but more slowly.
References:
1.  Kuo, T.-T. and Tu, J. Enzymatic synthesis of deoxy-5-methyl-cytidylic acid replacing deoxycytidylic acid in Xanthomonas oryzae phage Xp12DNA. Nature 263 (1976) 615. [PMID: 980110]
[EC 2.1.1.54 created 1978]
 
 
EC 2.1.1.55     
Accepted name: tRNA (adenine-N6-)-methyltransferase
Reaction: S-adenosyl-L-methionine + tRNA = S-adenosyl-L-homocysteine + tRNA containing N6-methyladenine
Other name(s): S-adenosyl-L-methionine:tRNA (adenine-6-N-)-methyltransferase
Systematic name: S-adenosyl-L-methionine:tRNA (adenine-N6-)-methyltransferase
References:
1.  Mandel, R., Hacker, B. and Maag, T.A. Altered transfer RNA methylase patterns in Marek's disease tumors. Cancer Res. 31 (1971) 613–616. [PMID: 4996578]
2.  Mittelman, A., Hall, R.H., Yohn, D.S. and Grace, J.T. The in vitro soluble RNA methylase activity of SV40-induced hamster tumors. Cancer Res. 27 (1967) 1409–1414. [PMID: 4292682]
3.  Sharma, O.K. Differences in the transfer RNA methyltransferases from normal rat liver and Novikoff hepatoma. Biochim. Biophys. Acta 299 (1973) 415–427. [PMID: 4349332]
[EC 2.1.1.55 created 1981]
 
 
EC 2.1.1.56     
Accepted name: mRNA (guanine-N7)-methyltransferase
Reaction: S-adenosyl-L-methionine + a 5′-(5′-triphosphoguanosine)-[mRNA] = S-adenosyl-L-homocysteine + a 5′-(N7-methyl 5′-triphosphoguanosine)-[mRNA]
Glossary: a 5′-(5′-triphosphoguanosine)-[mRNA] = G5′ppp5′R-[mRNA]
a 5′-(N7-methyl 5′-triphosphoguanosine)-[mRNA] = m7G5′ppp5′R-[mRNA] = cap0
Other name(s): messenger ribonucleate guanine 7-methyltransferase; guanine-7-methyltransferase; messenger RNA guanine 7-methyltransferase; S-adenosyl-L-methionine:mRNA (guanine-7-N)-methyltransferase
Systematic name: S-adenosyl-L-methionine:mRNA (guanine-N7)-methyltransferase
Comments: The nucleoside next to the terminal guanosine may be either guanosine or adenosine.
References:
1.  Ensinger, M.J., Martin, S.A., Paoletti, E. and Moss, B. Modification of the 5′-terminus of mRNA by soluble guanylyl and methyl transferases from vaccinia virus. Proc. Natl. Acad. Sci. USA 72 (1975) 2525–2529. [PMID: 1058472]
2.  Groner, Y., Gilbao, E. and Aviv, H. Methylation and capping of RNA polymerase II primary transcripts by HeLa nuclear homogenates. Biochemistry 17 (1978) 977–982. [PMID: 629955]
3.  Martin, S.A. and Moss, B. Modification of RNA by mRNA guanylyltransferase and mRNA(guanine-7-)methyltransferase from vaccinia virions. J. Biol. Chem. 250 (1975) 9330–9335. [PMID: 1194287]
4.  Martin, S.A., Paoletti, E. and Moss, B. Purification of mRNA guanylyltransferase and mRNA(guanine-7-)methyltransferase from vaccinia virions. J. Biol. Chem. 250 (1975) 9322–9329. [PMID: 1194286]
[EC 2.1.1.56 created 1981]
 
 
EC 2.1.1.57     
Accepted name: methyltransferase cap1
Reaction: S-adenosyl-L-methionine + a 5′-(N7-methyl 5′-triphosphoguanosine)-(purine-ribonucleotide)-[mRNA] = S-adenosyl-L-homocysteine + a 5′-(N7-methyl 5′-triphosphoguanosine)-(2′-O-methyl-purine-ribonucleotide)-[mRNA]
Other name(s): messenger ribonucleate nucleoside 2′-methyltransferase; messenger RNA (nucleoside-2′-)-methyltransferase; MTR1; cap1-MTase; mRNA (nucleoside-2′-O)-methyltransferase (ambiguous); S-adenosyl-L-methionine:mRNA (nucleoside-2′-O)-methyltransferase
Systematic name: S-adenosyl-L-methionine:5-(N7-methyl 5-triphosphoguanosine)-(purine-ribonucleotide)-[mRNA] 2-O-methyltransferase
Comments: This enzyme catalyses the methylation of the ribose on the first transcribed nucleotide of mRNA or snRNA molecules, which may be either guanosine or adenosine. This methylation event is known as cap1, and occurrs in all mRNAs and snRNAs of higher eukaryotes, including insects, vertebrates and their viruses. The human enzyme can also methylate mRNA molecules that lack methylation on the capping 5′-triphosphoguanosine [6].
References:
1.  Barbosa, E. and Moss, B. mRNA(nucleoside-2′-)-methyltransferase from vaccinia virus. Purification and physical properties. J. Biol. Chem. 253 (1978) 7692–7697. [PMID: 701281]
2.  Barbosa, E. and Moss, B. mRNA(nucleoside-2′-)-methyltransferase from vaccinia virus. Characteristics and substrate specificity. J. Biol. Chem. 253 (1978) 7698–7702. [PMID: 701282]
3.  Boone, R.F., Ensinger, M.J. and Moss, B. Synthesis of mRNA guanylyltransferase and mRNA methyltransferases in cells infected with vaccinia virus. J. Virol. 21 (1977) 475–483. [PMID: 833934]
4.  Ensinger, M.J., Martin, S.A., Paoletti, E. and Moss, B. Modification of the 5′-terminus of mRNA by soluble guanylyl and methyl transferases from vaccinia virus. Proc. Natl. Acad. Sci. USA 72 (1975) 2525–2529. [PMID: 1058472]
5.  Groner, Y., Gilbao, E. and Aviv, H. Methylation and capping of RNA polymerase II primary transcripts by HeLa nuclear homogenates. Biochemistry 17 (1978) 977–982. [PMID: 629955]
6.  Werner, M., Purta, E., Kaminska, K.H., Cymerman, I.A., Campbell, D.A., Mittra, B., Zamudio, J.R., Sturm, N.R., Jaworski, J. and Bujnicki, J.M. 2′-O-ribose methylation of cap2 in human: function and evolution in a horizontally mobile family. Nucleic Acids Res. 39 (2011) 4756–4768. [PMID: 21310715]
[EC 2.1.1.57 created 1981 (EC 2.1.1.58 created 1981, incorporated 1984), modified 2014]
 
 
EC 2.1.1.58      
Deleted entry: mRNA (adenosine-2′-O-)-methyltransferase. Now included with EC 2.1.1.57, mRNA (nucleoside-2′-O-)-methyltransferase
[EC 2.1.1.58 created 1981, deleted 1984]
 
 
EC 2.1.1.59     
Accepted name: [cytochrome c]-lysine N-methyltransferase
Reaction: S-adenosyl-L-methionine + [cytochrome c]-L-lysine = S-adenosyl-L-homocysteine + [cytochrome c]-N6-methyl-L-lysine
Other name(s): cytochrome c (lysine) methyltransferase; cytochrome c methyltransferase; cytochrome c-specific protein methylase III; cytochrome c-specific protein-lysine methyltransferase; S-adenosyl-L-methionine:[cytochrome c]-L-lysine 6-N-methyltransferase
Systematic name: S-adenosyl-L-methionine:[cytochrome c]-L-lysine N6-methyltransferase
Comments: One of a group of enzymes methylating proteins; see also EC 2.1.1.43 histone-lysine N-methyltransferase and EC 2.1.1.60 calmodulin-lysine N-methyltransferase.
References:
1.  Durban, E., Nochumson, S., Kim, S. and Paik, W.K. Cytochrome c-specific protein-lysine methyltransferase from Neurospora crassa. Purification, characterization, and substrate requirements. J. Biol. Chem. 253 (1978) 1427–1435. [PMID: 203592]
2.  Nochumson, S., Durban, E., Sangduk, K. and Paik, W.K. Cytochrome c-specific protein methylase III from Neurospora crassa. Biochem. J. 165 (1977) 11–18. [PMID: 196592]
3.  Valentine, J. and Pettigrew, G.W. A cytochrome c methyltransferase from Crithidia oncopelti. Biochem. J. 201 (1982) 329–338. [PMID: 6282265]
[EC 2.1.1.59 created 1982, modified 1983]
 
 
EC 2.1.1.60     
Accepted name: calmodulin-lysine N-methyltransferase
Reaction: S-adenosyl-L-methionine + calmodulin L-lysine = S-adenosyl-L-homocysteine + calmodulin N6-methyl-L-lysine
Other name(s): S-adenosylmethionine:calmodulin (lysine) N-methyltransferase; S-adenosyl-L-methionine:calmodulin-L-lysine 6-N-methyltransferase
Systematic name: S-adenosyl-L-methionine:calmodulin-L-lysine N6-methyltransferase
Comments: One of a group of enzymes methylating proteins; see also EC 2.1.1.43 histone-lysine N-methyltransferase and EC 2.1.1.59 [cytochrome-c]-lysine N-methyltransferase.
References:
1.  Sitaramayya, A., Wright, L.S. and Siegel, F.L. Enzymatic methylation of calmodulin in rat brain cytosol. J. Biol. Chem. 255 (1980) 8894–8900. [PMID: 6773954]
[EC 2.1.1.60 created 1982, modified 1983]
 
 
EC 2.1.1.61     
Accepted name: tRNA (5-methylaminomethyl-2-thiouridylate)-methyltransferase
Reaction: S-adenosyl-L-methionine + tRNA containing 5-aminomethyl-2-thiouridine = S-adenosyl-L-homocysteine + tRNA containing 5-methylaminomethyl-2-thiouridylate
Other name(s): transfer ribonucleate 5-methylaminomethyl-2-thiouridylate 5-methyltransferase; tRNA 5-methylaminomethyl-2-thiouridylate 5′-methyltransferase
Systematic name: S-adenosyl-L-methionine:tRNA (5-methylaminomethyl-2-thio-uridylate)-methyltransferase
Comments: This enzyme is specific for the terminal methyl group of 5-methylaminomethyl-2-thiouridylate.
References:
1.  Taya, Y. and Nishimura, S. Biosynthesis of 5-methylaminomethyl-2-thiouridylate. I. Isolation of a new tRNA-methylase specific for 5-methylaminomethyl-2-thiouridylate. Biochem. Biophys. Res. Commun. 51 (1973) 1062–1068. [PMID: 4703553]
2.  Taya, Y. and Nishimura, S. In: Salvatore, F., Borek, E., Zappia, V., Williams-Ashman, H.G. and Schlenk, F. (Ed.), The Biochemistry of Adenosylmethionine, Columbia University Press, New York, 1977, p. 251.
[EC 2.1.1.61 created 1982, modified 2012]
 
 
EC 2.1.1.62     
Accepted name: mRNA (2′-O-methyladenosine-N6-)-methyltransferase
Reaction: S-adenosyl-L-methionine + a 5-(N7-methyl 5-triphosphoguanosine)-2′-O-methyladenosine-[mRNA] = S-adenosyl-L-homocysteine + a 5-(N7-methyl 5-triphosphoguanosine)-N6,2′-O-dimethyladenosine-[mRNA]
Glossary: a 5-(N7-methyl 5-triphosphoguanosine)-2′-O-methyladenosine-[mRNA] = m7G(5′)pppAm-[mRNA]
a 5-(N7-methyl 5-triphosphoguanosine)-N6,2′-O-dimethyladenosine-[mRNA] = m7G(5′)pppm6Am-[mRNA]
Other name(s): messenger ribonucleate 2′-O-methyladenosine NG-methyltransferase; S-adenosyl-L-methionine:mRNA (2′-O-methyladenosine-6-N-)-methyltransferase
Systematic name: S-adenosyl-L-methionine:mRNA (2′-O-methyladenosine-N6-)-methyltransferase
References:
1.  Keith, J.M., Ensinger, M.J. and Moss, B. HeLa cell RNA (2′-O-methyladenosine-N6-)-methyltransferase specific for the capped 5′-end of messenger RNA. J. Biol. Chem. 253 (1978) 5033–5039. [PMID: 670176]
2.  Mauer, J., Luo, X., Blanjoie, A., Jiao, X., Grozhik, A.V., Patil, D.P., Linder, B., Pickering, B.F., Vasseur, J.J., Chen, Q., Gross, S.S., Elemento, O., Debart, F., Kiledjian, M. and Jaffrey, S.R. Reversible methylation of m6Am in the 5′ cap controls mRNA stability. Nature 541 (2017) 371–375. [PMID: 28002401]
[EC 2.1.1.62 created 1982]
 
 
EC 2.1.1.63     
Accepted name: methylated-DNA—[protein]-cysteine S-methyltransferase
Reaction: (1) DNA (containing 6-O-methylguanine) + protein L-cysteine = DNA (without 6-O-methylguanine) + protein S-methyl-L-cysteine
(2) DNA (containing 4-O-methylthymine) + protein L-cysteine = DNA (without 4-O-methylthymine) + protein S-methyl-L-cysteine
Other name(s): ada (gene name); ogt (gene name); MGT1 (gene name); MGMT (gene name)
Systematic name: DNA-6-O-methylguanine/DNA-4-O-methylthymine:[protein]-L-cysteine S-methyltransferase
Comments: This protein is involved in the repair of methylated DNA. Unlike EC 3.2.2.20, DNA-3-methyladenine glycosidase I and EC 3.2.2.21, DNA-3-methyladenine glycosidase II, which remove the methylated base leaving an apurinic/apyrimidinic site, this enzyme transfers the methyl group from the methylated DNA to an internal cysteine residue, leaving an intact nucleotide. Since the methyl transfer is irreversible, the enzyme can only catalyse a single turnover.
References:
1.  Foote, R.S., Mitra, S. and Pal, B.C. Demethylation of O6-methylguanine in a synthetic DNA polymer by an inducible activity in Escherichia coli. Biochem. Biophys. Res. Commun. 97 (1980) 654–659. [PMID: 7008792]
2.  Olsson, M. and Lindehl, T. Repair of alkylated DNA in Escherichia coli. Methyl group transfer from O6-methylguanine to a protein cysteine residue. J. Biol. Chem. 255 (1980) 10569–10571. [PMID: 7000780]
3.  McCarthy, T.V. and Lindahl, T. Methyl phosphotriesters in alkylated DNA are repaired by the Ada regulatory protein of E. coli. Nucleic Acids Res. 13 (1985) 2683–2698. [PMID: 2987862]
4.  Potter, P.M., Wilkinson, M.C., Fitton, J., Carr, F.J., Brennand, J., Cooper, D.P. and Margison, G.P. Characterisation and nucleotide sequence of ogt, the O6-alkylguanine-DNA-alkyltransferase gene of E. coli. Nucleic Acids Res. 15 (1987) 9177–9193. [PMID: 2825131]
5.  Rebeck, G.W., Smith, C.M., Goad, D.L. and Samson, L. Characterization of the major DNA repair methyltransferase activity in unadapted Escherichia coli and identification of a similar activity in Salmonella typhimurium. J. Bacteriol. 171 (1989) 4563–4568. [PMID: 2670886]
6.  Koike, G., Maki, H., Takeya, H., Hayakawa, H. and Sekiguchi, M. Purification, structure, and biochemical properties of human O6-methylguanine-DNA methyltransferase. J. Biol. Chem. 265 (1990) 14754–14762. [PMID: 2394694]
7.  Sassanfar, M., Dosanjh, M.K., Essigmann, J.M. and Samson, L. Relative efficiencies of the bacterial, yeast, and human DNA methyltransferases for the repair of O6-methylguanine and O4-methylthymine. Suggestive evidence for O4-methylthymine repair by eukaryotic methyltransferases. J. Biol. Chem. 266 (1991) 2767–2771. [PMID: 1993655]
8.  Xiao, W., Derfler, B., Chen, J. and Samson, L. Primary sequence and biological functions of a Saccharomyces cerevisiae O6-methylguanine/O4-methylthymine DNA repair methyltransferase gene. EMBO J. 10 (1991) 2179–2186. [PMID: 2065659]
[EC 2.1.1.63 created 1982, modified 1983, modified 1999, modified 2003, modified 2017]
 
 
EC 2.1.1.64     
Accepted name: 3-demethylubiquinol 3-O-methyltransferase
Reaction: S-adenosyl-L-methionine + 3-demethylubiquinol-n = S-adenosyl-L-homocysteine + ubiquinol-n
Glossary: 3-demethylubiquinol-n = 3-hydroxy-2-methoxy-5-methyl-6-(all-trans-polyprenyl)-1,4-benzoquinol
Other name(s): 5-demethylubiquinone-9 methyltransferase; OMHMB-methyltransferase; 2-octaprenyl-3-methyl-5-hydroxy-6-methoxy-1,4-benzoquinone methyltransferase; S-adenosyl-L-methionine:2-octaprenyl-3-methyl-5-hydroxy-6-methoxy-1,4-benzoquinone-O-methyltransferase; COQ3 (gene name); Coq3 O-methyltransferase; 3-demethylubiquinone-9 3-methyltransferase; ubiG (gene name, ambiguous)
Systematic name: S-adenosyl-L-methionine:3-hydroxy-2-methoxy-5-methyl-6-(all-trans-polyprenyl)-1,4-benzoquinol 3-O-methyltransferase
Comments: This enzyme is involved in ubiquinone biosynthesis. Ubiquinones from different organisms have a different number of prenyl units (for example, ubiquinone-6 in Saccharomyces, ubiquinone-9 in rat and ubiquinone-10 in human), and thus the natural substrate for the enzymes from different organisms has a different number of prenyl units. However, the enzyme usually shows a low degree of specificity regarding the number of prenyl units. For example, the human COQ3 enzyme can restore biosynthesis of ubiquinone-6 in coq3 deletion mutants of yeast [3]. The enzymes from yeast, Escherichia coli and rat also catalyse the methylation of 3,4-dihydroxy-5-all-trans-polyprenylbenzoate [3] (a reaction that is classified as EC 2.1.1.114, polyprenyldihydroxybenzoate methyltransferase).
References:
1.  Houser, R.M. and Olson, R.E. 5-Demethylubiquinone-9-methyltransferase from rat liver mitochondria. Characterization, localization, and solubilization. J. Biol. Chem. 252 (1977) 4017–4021. [PMID: 863914]
2.  Leppik, R.A., Stroobant, P., Shineberg, B., Young, I.G. and Gibson, F. Membrane-associated reactions in ubiquinone biosynthesis. 2-Octaprenyl-3-methyl-5-hydroxy-6-methoxy-1,4-benzoquinone methyltransferase. Biochim. Biophys. Acta 428 (1976) 146–156. [PMID: 769831]
3.  Poon, W.W., Barkovich, R.J., Hsu, A.Y., Frankel, A., Lee, P.T., Shepherd, J.N., Myles, D.C. and Clarke, C.F. Yeast and rat Coq3 and Escherichia coli UbiG polypeptides catalyze both O-methyltransferase steps in coenzyme Q biosynthesis. J. Biol. Chem. 274 (1999) 21665–21672. [PMID: 10419476]
4.  Jonassen, T. and Clarke, C.F. Isolation and functional expression of human COQ3, a gene encoding a methyltransferase required for ubiquinone biosynthesis. J. Biol. Chem. 275 (2000) 12381–12387. [PMID: 10777520]
[EC 2.1.1.64 created 1982, modified 2011]
 
 
EC 2.1.1.65     
Accepted name: licodione 2′-O-methyltransferase
Reaction: S-adenosyl-L-methionine + licodione = S-adenosyl-L-homocysteine + 2′-O-methyllicodione
Systematic name: S-adenosyl-L-methionine:licodione 2′-O-methyltransferase
Comments: As well as licodione [1-(2,4-dihydroxyphenyl)-3-(4-hydroxyphenyl)-1,3-propanedione], the 2′′-hydroxy-derivative and isoliquiritigenin can act as acceptors, but more slowly.
References:
1.  Ayabe, S.-I., Yoshikawa, T., Kobayashi, M. and Furuya, T. Biosynthesis of retrochalcone, echinatin: involvement of O-methyltransferase to licodione. Phytochemistry 19 (1980) 2331–2336.
[EC 2.1.1.65 created 1983]
 
 
EC 2.1.1.66      
Deleted entry: rRNA (adenosine-2′-O-)-methyltransferase. Now covered by EC 2.1.1.230, 23S rRNA (adenosine1067-2-O)-methyltransferase.
[EC 2.1.1.66 created 1984, deleted 2013]
 
 
EC 2.1.1.67     
Accepted name: thiopurine S-methyltransferase
Reaction: S-adenosyl-L-methionine + a thiopurine = S-adenosyl-L-homocysteine + a thiopurine S-methylether
Other name(s): mercaptopurine methyltransferase; thiopurine methyltransferase; 6-thiopurine transmethylase; TPMT
Systematic name: S-adenosyl-L-methionine:thiopurine S-methyltransferase
Comments: Also acts, more slowly, on thiopyrimidines and aromatic thiols. Not identical with EC 2.1.1.9 thiol S-methyltransferase.
References:
1.  Remy, C.N. Metabolism of thiopyrimidines and thiopurines. S-Methylation with S-adenosylmethionine transmethylase and catabolism in mammalian tissues. J. Biol. Chem. 238 (1963) 1078–1084. [PMID: 13981612]
2.  Woodson, L.C., Ames, M.M., Selassie, C.D, Hansch, C. and Weinshilbaum, R.M. Thiopurine methyltransferase. Aromatic thiol substrates and inhibition by benzoic acid derivatives. Mol. Pharmacol. 24 (1983) 471–478. [PMID: 6633508]
3.  Woodson, L.C. and Weinshilbaum, R.M. Human kidney thiopurine methyltransferase. Purification and biochemical properties. Biochem. Pharmacol. 32 (1983) 819–826. [PMID: 6838629]
[EC 2.1.1.67 created 1984]
 
 
EC 2.1.1.68     
Accepted name: caffeate O-methyltransferase
Reaction: S-adenosyl-L-methionine + 3,4-dihydroxy-trans-cinnamate = S-adenosyl-L-homocysteine + 3-methoxy-4-hydroxy-trans-cinnamate
Other name(s): caffeate methyltransferase; caffeate 3-O-methyltransferase; S-adenosyl-L-methionine:caffeic acid-O-methyltransferase
Systematic name: S-adenosyl-L-methionine:3,4-dihydroxy-trans-cinnamate 3-O-methyltransferase
Comments: 3,4-Dihydroxybenzaldehyde and catechol can act as acceptors, but more slowly.
References:
1.  Ebel, J., Schaller-Hekeler, B., Knobloch, K.-H., Wellman, E., Grisebach, H. and Hahlbrock, K. Coordinated changes in enzyme activities of phenylpropanoid metabolism during the growth of soybean cell suspension cultures. Biochim. Biophys. Acta 362 (1974) 417–424. [PMID: 4472044]
2.  Poulton, J.E. and Butt, V.S. Purification and properties of S-adenosyl-L-methionine: caffeic acid O-methyltransferase from leaves of spinach beet (Beta vulgaris L). Biochim. Biophys. Acta 403 (1975) 301–314. [PMID: 241400]
3.  Shimada, M., Kuroda, H. and Higuchi, T. Evidence for the formation of methoxyl groups of ferulic and sinapic acid in Bambusa by the same O-methyltransferase. Phytochemistry 12 (1973) 2873–2875.
[EC 2.1.1.68 created 1984]
 
 
EC 2.1.1.69     
Accepted name: 5-hydroxyfuranocoumarin 5-O-methyltransferase
Reaction: (1) S-adenosyl-L-methionine + a 5-hydroxyfurocoumarin = S-adenosyl-L-homocysteine + a 5-methoxyfurocoumarin (general reaction)
(2) S-adenosyl-L-methionine + bergaptol = S-adenosyl-L-homocysteine + bergapten
Glossary: bergaptol = 5-hydroxypsoralen
O-methylbergaptol = bergapten = 5-methoxypsoralen
Other name(s): furanocoumarin 5-methyltransferase; furanocoumarin 5-O-methyltransferase; bergaptol 5-O-methyltransferase; bergaptol O-methyltransferase; bergaptol methyltransferase; S-adenosyl-L-methionine:bergaptol O-methyltransferase; BMT; S-adenosyl-L-methionine:5-hydroxyfuranocoumarin 5-O-methyltransferase
Systematic name: S-adenosyl-L-methionine:5-hydroxyfurocoumarin 5-O-methyltransferase
Comments: Converts bergaptol into bergapten, which has therapeutic potential in the treatment of psoriasis as it has photosensitizing and antiproliferative activities [4]. The enzyme methylates the 5-hydroxy group of some hydroxy- and methylcoumarins, such as 5-hydroxyxanthotoxin [3], but has little activity on non-coumarin phenols [1]. Caffeate, 5-hydroxyferulate and daphnetin are not substrates [4]. Cu2+, Zn2+ and Co2+ cause enzyme inhibition [4]. (see also EC 2.1.1.70, 8-hydroxyfuranocoumarin 8-O-methyltransferase)
References:
1.  Thompson, H.J., Sharma, S.K. and Brown, S.A. O-Methyltransferases of furanocoumarin biosynthesis. Arch. Biochem. Biophys. 188 (1978) 272–281. [PMID: 28084]
2.  Sharma, S.K., Garrett, J.M. and Brown, S.A. Separation of the S-adenosylmethionine: 5- and 8-hydroxyfuranocoumarin O-methyltransferases of Ruta graveolens L. by general ligand affinity chromatography. Z. Naturforsch. [C] 34C (1979) 387–391. [PMID: 156999]
3.  Hauffe, K.D., Hahlbrock, K. and Scheel, D. Elicitor-stimulated furanocoumarin biosynthesis in cultured parsley cells - S-adenosyl-L-methionine-bergaptol and S-adenosyl-L-methionine-xanthotoxol O-methyltransferases. Z. Naturforsch. C: Biosci. 41 (1986) 228–239.
4.  Hehmann, M., Lukačin, R., Ekiert, H. and Matern, U. Furanocoumarin biosynthesis in Ammi majus L. Cloning of bergaptol O-methyltransferase. Eur. J. Biochem. 271 (2004) 932–940. [PMID: 15009205]
[EC 2.1.1.69 created 1984 (EC 2.1.1.92 created 1989, incorporated 2006), modified 2006]
 
 
EC 2.1.1.70     
Accepted name: 8-hydroxyfuranocoumarin 8-O-methyltransferase
Reaction: (1) S-adenosyl-L-methionine + an 8-hydroxyfurocoumarin = S-adenosyl-L-homocysteine + an 8-methoxyfurocoumarin (general reaction)
(2) S-adenosyl-L-methionine + xanthotoxol = S-adenosyl-L-homocysteine + xanthotoxin
Glossary: xanthotoxin = O-methylxanthotoxol = 8-methoxypsoralen
xanthotoxol = 8-hydroxypsoralen
Other name(s): furanocoumarin 8-methyltransferase; furanocoumarin 8-O-methyl-transferase; xanthotoxol 8-O-methyltransferase; XMT; 8-hydroxyfuranocoumarin 8-O-methyltransferase; SAM:xanthotoxol O-methyltransferase; S-adenosyl-L-methionine:8-hydroxyfuranocoumarin 8-O-methyltransferase; xanthotoxol methyltransferase; xanthotoxol O-methyltransferase; S-adenosyl-L-methionine:xanthotoxol O-methyltransferase; S-adenosyl-L-methionine-xanthotoxol O-methyltransferase
Systematic name: S-adenosyl-L-methionine:8-hydroxyfurocoumarin 8-O-methyltransferase
Comments: Converts xanthotoxol into xanthotoxin, which has therapeutic potential in the treatment of psoriasis as it has photosensitizing and antiproliferative activities [4]. Methylates the 8-hydroxy group of some hydroxy- and methylcoumarins, but has little activity on non-coumarin phenols (see also EC 2.1.1.69, 5-hydroxyfuranocoumarin 5-O-methyltransferase).
References:
1.  Thompson, H.J., Sharma, S.K. and Brown, S.A. O-Methyltransferases of furanocoumarin biosynthesis. Arch. Biochem. Biophys. 188 (1978) 272–281. [PMID: 28084]
2.  Hauffe, K.D., Hahlbrock, K. and Scheel, D. Elicitor-stimulated furanocoumarin biosynthesis in cultured parsley cells - S-adenosyl-L-methionine-bergaptol and S-adenosyl-L-methionine-xanthotoxol O-methyltransferases. Z. Naturforsch. C: Biosci. 41 (1986) 228–239.
3.  Sharma, S.K., Garrett, J.M. and Brown, S.A. Separation of the S-adenosylmethionine: 5- and 8-hydroxyfuranocoumarin O-methyltransferases of Ruta graveolens L. by general ligand affinity chromatography. Z. Naturforsch. [C] 34C (1979) 387–391. [PMID: 156999]
4.  Hehmann, M., Lukačin, R., Ekiert, H. and Matern, U. Furanocoumarin biosynthesis in Ammi majus L. Cloning of bergaptol O-methyltransferase. Eur. J. Biochem. 271 (2004) 932–940. [PMID: 15009205]
[EC 2.1.1.70 created 1984, modified 2006 (EC 2.1.1.93 created 2006, incorporated 2008)]
 
 
EC 2.1.1.71     
Accepted name: phosphatidyl-N-methylethanolamine N-methyltransferase
Reaction: S-adenosyl-L-methionine + phosphatidyl-N-methylethanolamine = S-adenosyl-L-homocysteine + phosphatidyl-N-dimethylethanolamine
Other name(s): phosphatidylmonomethylethanolamine methyltransferase; methyltransferase II; phospholipid methyltransferase; PLMT; phosphatidyl-N-methylethanolamine methyltransferase; phosphatidyl-N-monomethylethanolamine methyltransferase; phosphatidylethanolamine methyltransferase I; phosphatidylmonomethylethanolamine methyltransferase
Systematic name: S-adenosyl-L-methionine:phosphatidyl-N-methylethanolamine N-methyltransferase
Comments: The enzyme also catalyses the transfer of a further methyl group, producing phosphatidylcholine.
References:
1.  Hirata, F., Viveros, O.H., Diliberto, E.J., Jr. and Axelrod, J. Identification and properties of two methyltransferases in conversion of phosphatidylethanolamine to phosphatidylcholine. Proc. Natl. Acad. Sci. USA 75 (1978) 1718–1721. [PMID: 25437]
2.  Schneider, W.J. and Vance, D.E. Conversion of phosphatidylethanolamine to phosphatidylcholine in rat liver. Partial purification and characterization of the enzymatic activities. J. Biol. Chem. 254 (1979) 3886–3891. [PMID: 438165]
[EC 2.1.1.71 created 1984]
 
 
EC 2.1.1.72     
Accepted name: site-specific DNA-methyltransferase (adenine-specific)
Reaction: S-adenosyl-L-methionine + adenine in DNA = S-adenosyl-L-homocysteine + N6-methyladenine in DNA
Other name(s): modification methylase; restriction-modification system
Systematic name: S-adenosyl-L-methionine:adenine in DNA N6-methyltransferase
Comments: This is a large group of enzymes, most of which form so-called ’restriction-modification systems’ with nucleases that possess similar site specificity [the nucleases are listed as either EC 3.1.21.3 (type 1 site-specific deoxyribonuclease), EC 3.1.21.4 (type II site-specific deoxyribonuclease) or EC 3.1.21.5 (type III site-specific deoxyribonuclease)]. A complete listing of all of these enzymes has been produced by R.J. Roberts and is available on-line at http://rebase.neb.com/rebase/rebase.html.
References:
1.  Kessler, C. and Manta, V. Specificity of restriction endonucleases and DNA modification methyltransferases: a review. Gene 92 (1990) 1–248. [PMID: 2172084]
2.  Roberts, R.J. Restriction enzymes and their isoschizomers. Nucleic Acids Res. 18 (1990) 2331–2365. [PMID: 2159140]
3.  Yuan, R. Structure and mechanism of multifunctional restriction endonucleases. Annu. Rev. Biochem. 50 (1981) 285–319. [PMID: 6267988]
[EC 2.1.1.72 created 1984]
 
 
EC 2.1.1.73      
Deleted entry:  site-specific DNA-methyltransferase (cytosine-specific). Reaction is that of EC 2.1.1.37, DNA (cytosine-5-)-methyltransferase
[EC 2.1.1.73 created 1984, deleted 2003]
 
 
EC 2.1.1.74     
Accepted name: methylenetetrahydrofolate—tRNA-(uracil54-C5)-methyltransferase [NAD(P)H-oxidizing]
Reaction: 5,10-methylenetetrahydrofolate + uracil54 in tRNA + NAD(P)H + H+ = tetrahydrofolate + 5-methyluracil54 in tRNA + NAD(P)+
Glossary: Ψ = pseudouridine
T = ribothymidine = 5-methyluridine
Other name(s): folate-dependent ribothymidyl synthase; methylenetetrahydrofolate-transfer ribonucleate uracil 5-methyltransferase; 5,10-methylenetetrahydrofolate:tRNA-UΨC (uracil-5-)-methyl-transferase; 5,10-methylenetetrahydrofolate:tRNA (uracil-5-)-methyl-transferase; TrmFO; folate/FAD-dependent tRNA T54 methyltransferase; methylenetetrahydrofolate—tRNA-(uracil54-C5)-methyltransferase (FADH2-oxidizing)
Systematic name: 5,10-methylenetetrahydrofolate:tRNA (uracil54-C5)-methyltransferase
Comments: A flavoprotein (FAD). Up to 25% of the bases in mature tRNA are post-translationally modified or hypermodified. One almost universal post-translational modification is the conversion of U54 into ribothymidine in the TΨC loop, and this modification is found in most species studied to date [2]. Unlike this enzyme, which uses 5,10-methylenetetrahydrofolate and NAD(P)H to supply the atoms for methylation of U54, EC 2.1.1.35, tRNA (uracil54-C5)-methyltransferase, uses S-adenosyl-L-methionine.
References:
1.  Delk, A.S., Nagle, D.P., Jr. and Rabinowitz, J.C. Methylenetetrahydrofolate-dependent biosynthesis of ribothymidine in transfer RNA of Streptococcus faecalis. Evidence for reduction of the 1-carbon unit by FADH2. J. Biol. Chem. 255 (1980) 4387–4390. [PMID: 6768721]
2.  Becker, H.F., Motorin, Y., Sissler, M., Florentz, C. and Grosjean, H. Major identity determinants for enzymatic formation of ribothymidine and pseudouridine in the TΨ-loop of yeast tRNAs. J. Mol. Biol. 274 (1997) 505–518. [PMID: 9417931]
3.  Nishimasu, H., Ishitani, R., Yamashita, K., Iwashita, C., Hirata, A., Hori, H. and Nureki, O. Atomic structure of a folate/FAD-dependent tRNA T54 methyltransferase. Proc. Natl. Acad. Sci. USA 106 (2009) 8180–8185. [PMID: 19416846]
4.  Yamagami, R., Yamashita, K., Nishimasu, H., Tomikawa, C., Ochi, A., Iwashita, C., Hirata, A., Ishitani, R., Nureki, O. and Hori, H. The tRNA recognition mechanism of folate/FAD-dependent tRNA methyltransferase (TrmFO). J. Biol. Chem. 287 (2012) 42480–42494. [PMID: 23095745]
[EC 2.1.1.74 created 1983 as EC 2.1.2.12, transferred 1984 to EC 2.1.1.74, modified 2011, modified 2019]
 
 
EC 2.1.1.75     
Accepted name: apigenin 4′-O-methyltransferase
Reaction: S-adenosyl-L-methionine + apigenin = S-adenosyl-L-homocysteine + acacetin
Glossary: apigenin = 4′,5,7-trihydroxyflavone
acacetin = 4′-methoxy-5,7-dihydroxyflavone
naringenin = 4′,5,7-trihydroxyflavan-4-one
Other name(s): flavonoid O-methyltransferase; flavonoid methyltransferase; S-adenosyl-L-methionine:5,7,4′-trihydroxyflavone 4′-O-methyltransferase
Systematic name: S-adenosyl-L-methionine:apigenin 4′-O-methyltransferase
Comments: Converts apigenin into acacetin. Naringenin can also act as an acceptor, but more slowly.
References:
1.  Kuroki, G. and Poulton, J.E. The para-O-methylation of apigenin to acacetin by cell-free extracts of Robinia pseudoacacia L. Z. Naturforsch. C: Biosci. 36 (1981) 916–920.
[EC 2.1.1.75 created 1984]
 
 
EC 2.1.1.76     
Accepted name: quercetin 3-O-methyltransferase
Reaction: S-adenosyl-L-methionine + 3,5,7,3′,4′-pentahydroxyflavone = S-adenosyl-L-homocysteine + 3-methoxy-5,7,3′,4′-tetrahydroxyflavone
Other name(s): flavonol 3-O-methyltransferase; flavonoid 3-methyltransferase
Systematic name: S-adenosyl-L-methionine:3,5,7,3′,4′-pentahydroxyflavone 3-O-methyltransferase
Comments: Specific for quercetin. Related enzymes bring about the 3-O-methylation of other flavonols, such as galangin and kaempferol.
References:
1.  De Luca, V., Brunet, G., Khouri, H., Ibrahim, R. and Hrazdina, G. Flavonol 3-O-methyltransferase in plant-tissues. Z. Naturforsch. 37 (1982) 134–135.
2.  De Luca, V. and Ibrahim, R.K. Enzymatic synthesis of polymethylated flavonols in Chrysosplenium americanum. I. Partial purification and some properties of S-adenosyl-L-methionine:flavonol 3-, 6-, 7-, and 4′-O-methyltransferases. Arch. Biochem. Biophys. 238 (1985) 596–605. [PMID: 3994393]
3.  De Luca, V. and Ibrahim, R.K. Enzymatic synthesis of polymethylated flavonols in Chrysosplenium americanum. II. Substrate interaction and product inhibition studies of flavonol 3-, 6-, and 4′-O-methyltransferases. Arch. Biochem. Biophys. 238 (1985) 606–618. [PMID: 3994394]
4.  Ibrahim, R.K. and De Luca, V. Polymethylated flavonol synthesis is catalyzed by distinct O-methyltransferases. Naturwissenschaften 69 (1982) 41–42.
[EC 2.1.1.76 created 1984]
 
 
EC 2.1.1.77     
Accepted name: protein-L-isoaspartate(D-aspartate) O-methyltransferase
Reaction: S-adenosyl-L-methionine + protein L-isoaspartate = S-adenosyl-L-homocysteine + protein L-isoaspartate α-methyl ester
Other name(s): protein-L-isoaspartate O-methyltransferase; protein-β-aspartate O-methyltransferase; D-aspartyl/L-isoaspartyl methyltransferase; L-isoaspartyl/D-aspartyl protein carboxyl methyltransferase; protein (D-aspartate) methyltransferase; protein D-aspartate methyltransferase; protein L-isoaspartate methyltransferase; protein L-isoaspartyl methyltransferase; protein O-methyltransferase (L-isoaspartate); L-aspartyl/L-isoaspartyl protein methyltransferase
Systematic name: S-adenosyl-L-methionine:protein-L-isoaspartate O-methyltransferase
Comments: D-Aspartate (but not L-aspartate) residues in proteins can also act as acceptors. Previously also listed as EC 2.1.1.24.
References:
1.  Aswad, D.W. and Johnson, B.A. The unusual substrate-specificity of eukaryotic protein carboxyl methyltransferases. Trends Biochem. Sci. 12 (1987) 155–158.
2.  Clarke, S. Protein carboxyl methyltransferases: two distinct classes of enzymes. Annu. Rev. Biochem. 54 (1985) 479–506. [PMID: 3896126]
3.  Kim, S. and Paik, W.K. Purification and properties of protein methylase II. J. Biol. Chem. 245 (1970) 1806–1813. [PMID: 5438363]
4.  Ota, I.M., Ding, L. and Clarke, S. Methylation at specific altered aspartyl and asparaginyl residues in glucagon by the erythrocyte protein carboxyl methyltransferase. J. Biol. Chem. 262 (1987) 8522–8531. [PMID: 3597386]
[EC 2.1.1.77 created 1984, modified 1989 (EC 2.1.1.24 created 1972, modified 1983, modified 1989, part incorporated 1992)]
 
 
EC 2.1.1.78     
Accepted name: isoorientin 3′-O-methyltransferase
Reaction: S-adenosyl-L-methionine + isoorientin = S-adenosyl-L-homocysteine + isoscoparin
Other name(s): isoorientin 3′-methyltransferase
Systematic name: S-adenosyl-L-methionine:isoorientin 3′-O-methyltransferase
Comments: Also acts on isoorientin 2′′-O-rhamnoside. Involved in the biosynthesis of flavones.
References:
1.  van Brederode, J., Kamps-Heinsbroek, R. and Mastenbroek, O. Biochemical and ontogenetic evidence that the ferulic acid and isoscoparin formation in silene are catalyzed by different enzymes. Z. Pflanzenphysiol. 106 (1982) 43–53.
[EC 2.1.1.78 created 1986]
 
 
EC 2.1.1.79     
Accepted name: cyclopropane-fatty-acyl-phospholipid synthase
Reaction: S-adenosyl-L-methionine + phospholipid olefinic fatty acid = S-adenosyl-L-homocysteine + phospholipid cyclopropane fatty acid
Other name(s): cyclopropane synthetase; unsaturated-phospholipid methyltransferase; cyclopropane synthase; cyclopropane fatty acid synthase; cyclopropane fatty acid synthetase; CFA synthase
Systematic name: S-adenosyl-L-methionine:unsaturated-phospholipid methyltransferase (cyclizing)
Comments: The enzyme adds a methylene group across the 9,10 position of a Δ9-olefinic acyl chain in phosphatidylethanolamine or, more slowly, phosphatidylglycerol or phosphatidylinositol, forming a cyclopropane derivative (cf. EC 2.1.1.16 methylene-fatty-acyl-phospholipid synthase).
References:
1.  Chung, A.E. and Law, J.H. Cyclopropane fatty acid synthetase: Partial purification and properties. Biochemistry 3 (1964) 967–974. [PMID: 14214089]
2.  Zalkin, H., Law, J.H. and Goldfine, H. Enzymatic synthesis of cyclopropane fatty acids catalyzed by bacterial extracts. J. Biol. Chem. 238 (1963) 1242–1248. [PMID: 14003136]
[EC 2.1.1.79 created 1986]
 
 
EC 2.1.1.80     
Accepted name: protein-glutamate O-methyltransferase
Reaction: S-adenosyl-L-methionine + protein L-glutamate = S-adenosyl-L-homocysteine + protein L-glutamate methyl ester
Other name(s): methyl-accepting chemotaxis protein O-methyltransferase; S-adenosylmethionine-glutamyl methyltransferase; methyl-accepting chemotaxis protein methyltransferase II; S-adenosylmethionine:protein-carboxyl O-methyltransferase; protein methylase II; MCP methyltransferase I; MCP methyltransferase II; protein O-methyltransferase; protein(aspartate)methyltransferase; protein(carboxyl)methyltransferase; protein carboxyl-methylase; protein carboxyl-O-methyltransferase; protein carboxylmethyltransferase II; protein carboxymethylase; protein carboxymethyltransferase; protein methyltransferase II
Systematic name: S-adenosyl-L-methionine:protein-L-glutamate O-methyltransferase
Comments: Forms ester groups with L-glutamate residues in a number of membrane proteins.
References:
1.  Burgess-Cassler, A., Ulla, A.H.J. and Ordal, G.W. Purification and characterization of Bacillus subtilis methyl-accepting chemotaxis protein methyltransferase II. J. Biol. Chem. 257 (1982) 8412–8417. [PMID: 6806296]
2.  Kleene, S.J., Toews, M.L. and Adler, J. Isolation of glutamic acid methyl ester from an Escherichia coli membrane protein involved in chemotaxis. J. Biol. Chem. 252 (1977) 3214–3218. [PMID: 16888]
3.  Simms, S.A., Stock, A.M. and Stock, J.B. Purification and characterization of the S-adenosylmethionine:glutamyl methyltransferase that modifies membrane chemoreceptor proteins in bacteria. J. Biol. Chem. 262 (1987) 8537–8543. [PMID: 3298235]
4.  Springer, W.R. and Koshland, D.E., Jr. Identification of a protein methyltransferase as the cheR gene product in the bacterial sensing system. Proc. Natl. Acad. Sci. USA 74 (1977) 533–537. [PMID: 322131]
[EC 2.1.1.80 created 1989 (EC 2.1.1.24 created 1972, modified 1983, modified 1989, part incorporated 1992)]
 
 
EC 2.1.1.81      
Deleted entry:  nicotine N-methyltransferase. Now included with EC 2.1.1.49 amine N-methyltransferase
[EC 2.1.1.81 created 1989, deleted 1990]
 
 
EC 2.1.1.82     
Accepted name: 3-methylquercetin 7-O-methyltransferase
Reaction: S-adenosyl-L-methionine + 5,7,3′,4′-tetrahydroxy-3-methoxyflavone = S-adenosyl-L-homocysteine + 5,3′,4′-trihydroxy-3,7-dimethoxyflavone
Other name(s): flavonol 7-O-methyltransferase; flavonol 7-methyltransferase; 7-OMT; S-adenosyl-L-methionine:3′,4′,5,7-tetrahydroxy-3-methoxyflavone 7-O-methyltransferase; 3-methylquercitin 7-O-methyltransferase [mis-spelt]
Systematic name: S-adenosyl-L-methionine:5,7,3′,4′-tetrahydroxy-3-methoxyflavone 7-O-methyltransferase
Comments: Involved with EC 2.1.1.76 quercetin 3-O-methyltransferase and EC 2.1.1.83 3,7-dimethylquercetin 4′-O-methyltransferase in the methylation of quercetin to 3,7,4′-trimethylquercetin in Chrysosplenium americanum. Does not act on flavones, dihydroflavonols, or their glucosides.
References:
1.  De Luca, V. and Ibrahim, R.K. Enzymatic synthesis of polymethylated flavonols in Chrysosplenium americanum. I. Partial purification and some properties of S-adenosyl-L-methionine:flavonol 3-, 6-, 7-, and 4′-O-methyltransferases. Arch. Biochem. Biophys. 238 (1985) 596–605. [PMID: 3994393]
[EC 2.1.1.82 created 1989]
 
 
EC 2.1.1.83     
Accepted name: 3,7-dimethylquercetin 4′-O-methyltransferase
Reaction: S-adenosyl-L-methionine + 5,3′,4′-trihydroxy-3,7-dimethoxyflavone = S-adenosyl-L-homocysteine + 5,3′-dihydroxy-3,7,4′-trimethoxyflavone
Other name(s): flavonol 4′-O-methyltransferase; flavonol 4′-methyltransferase; 4′-OMT; S-adenosyl-L-methionine:3′,4′,5-trihydroxy-3,7-dimethoxyflavone 4′-O-methyltransferase; 3,7-dimethylquercitin 4′-O-methyltransferase [mis-spelt]
Systematic name: S-adenosyl-L-methionine:5,3′,4′-trihydroxy-3,7-dimethoxyflavone 4′-O-methyltransferase
Comments: 3,7-Dimethylquercetagetin can also act as acceptor. Involved with EC 2.1.1.76 quercetin 3-O-methyltransferase and EC 2.1.1.82 3-methylquercetin 7-O-methyltransferase in the methylation of quercetin to 3,7,4′-trimethylquercetin in Chrysosplenium americanum. Does not act on flavones, dihydroflavonols, or their glucosides.
References:
1.  De Luca, V. and Ibrahim, R.K. Enzymatic synthesis of polymethylated flavonols in Chrysosplenium americanum. I. Partial purification and some properties of S-adenosyl-L-methionine:flavonol 3-, 6-, 7-, and 4′-O-methyltransferases. Arch. Biochem. Biophys. 238 (1985) 596–605. [PMID: 3994393]
2.  De Luca, V. and Ibrahim, R.K. Enzymatic synthesis of polymethylated flavonols in Chrysosplenium americanum. II. Substrate interaction and product inhibition studies of flavonol 3-, 6-, and 4′-O-methyltransferases. Arch. Biochem. Biophys. 238 (1985) 606–618. [PMID: 3994394]
[EC 2.1.1.83 created 1989]
 
 
EC 2.1.1.84     
Accepted name: methylquercetagetin 6-O-methyltransferase
Reaction: S-adenosyl-L-methionine + 5,6,3′,4′-tetrahydroxy-3,7-dimethoxyflavone = S-adenosyl-L-homocysteine + 5,3′,4′-trihydroxy-3,6,7-trimethoxyflavone
Other name(s): flavonol 6-O-methyltransferase; flavonol 6-methyltransferase; 6-OMT; S-adenosyl-L-methionine:3′,4′,5,6-tetrahydroxy-3,7-dimethoxyflavone 6-O-methyltransferase
Systematic name: S-adenosyl-L-methionine:5,6,3′,4′-tetrahydroxy-3,7-dimethoxyflavone 6-O-methyltransferase
Comments: The enzymes from Chrysosplenium americanum also methylates 3,7,3′-trimethylquercetagetin at the 6-position. Does not act on flavones, dihydroflavonols, or their glucosides.
References:
1.  De Luca, V. and Ibrahim, R.K. Enzymatic synthesis of polymethylated flavonols in Chrysosplenium americanum. I. Partial purification and some properties of S-adenosyl-L-methionine:flavonol 3-, 6-, 7-, and 4′-O-methyltransferases. Arch. Biochem. Biophys. 238 (1985) 596–605. [PMID: 3994393]
2.  De Luca, V. and Ibrahim, R.K. Enzymatic synthesis of polymethylated flavonols in Chrysosplenium americanum. II. Substrate interaction and product inhibition studies of flavonol 3-, 6-, and 4′-O-methyltransferases. Arch. Biochem. Biophys. 238 (1985) 606–618. [PMID: 3994394]
[EC 2.1.1.84 created 1989]
 
 
EC 2.1.1.85     
Accepted name: protein-histidine N-methyltransferase
Reaction: S-adenosyl-L-methionine + protein L-histidine = S-adenosyl-L-homocysteine + protein Nτ-methyl-L-histidine
Other name(s): protein methylase IV; protein (histidine) methyltransferase; actin-specific histidine methyltransferase; S-adenosyl methionine:protein-histidine N-methyltransferase
Systematic name: S-adenosyl-L-methionine:protein-L-histidine N-tele-methyltransferase
Comments: Highly specific for histidine residues, for example, in actin.
References:
1.  Vijayasarathy, C. and Narasinga Rao, B.S. Partial purification and characterisation of S-adenosylmethionine:protein-histidine N-methyltransferase from rabbit skeletal muscle. Biochim. Biophys. Acta 923 (1987) 156–165. [PMID: 3801515]
[EC 2.1.1.85 created 1989]
 
 
EC 2.1.1.86     
Accepted name: tetrahydromethanopterin S-methyltransferase
Reaction: 5-methyl-5,6,7,8-tetrahydromethanopterin + CoM + 2 Na+in = 5,6,7,8-tetrahydromethanopterin + 2-(methylsulfanyl)ethane-1-sulfonate + 2 Na+out
Glossary: CoM = coenzyme M = 2-sulfanylethane-1-sulfonate
tetrahydromethanopterin = 1-(4-{(1R)-1-[(6S,7S)-2-amino-7-methyl-4-oxo-3,4,5,6,7,8-hexahydropteridin-6-yl]ethylamino}phenyl)-1-deoxy-5-O-{5-O-[(1S)-1,3-dicarboxypropylphosphonato]-α-D-ribofuranosyl}-D-ribitol
Other name(s): tetrahydromethanopterin methyltransferase; mtrA-H (gene names); cmtA (gene name); N5-methyltetrahydromethanopterin—coenzyme M methyltransferase; 5-methyl-5,6,7,8-tetrahydromethanopterin:2-mercaptoethanesulfonate 2-methyltransferase
Systematic name: 5-methyl-5,6,7,8-tetrahydromethanopterin:CoM 2-methyltransferase (Na+-transporting)
Comments: Involved in the formation of methane from CO2 in methanogenic archaea. The reaction involves the export of one or two sodium ions. The enzyme from the archaeon Methanobacterium thermoautotrophicum is a membrane-associated multienzyme complex composed of eight different subunits, and contains a 5′-hydroxybenzimidazolyl-cobamide prosthetic group, to which the methyl group is attached during the transfer. A soluble enzyme that is induced by the presence of CO has been reported as well [6].
References:
1.  Sauer, F.D. Tetrahydromethanopterin methyltransferase, a component of the methane synthesizing complex of Methanobacterium thermoautotrophicum. Biochem. Biophys. Res. Commun. 136 (1986) 542–547. [PMID: 3085670]
2.  Gartner, P., Ecker, A., Fischer, R., Linder, D., Fuchs, G. and Thauer, R.K. Purification and properties of N5-methyltetrahydromethanopterin:coenzyme M methyltransferase from Methanobacterium thermoautotrophicum. Eur. J. Biochem. 213 (1993) 537–545. [PMID: 8477726]
3.  Weiss, D.S., Gartner, P. and Thauer, R.K. The energetics and sodium-ion dependence of N5-methyltetrahydromethanopterin:coenzyme M methyltransferase studied with cob(I)alamin as methyl acceptor and methylcob(III)alamin as methyl donor. Eur. J. Biochem. 226 (1994) 799–809. [PMID: 7813469]
4.  Harms, U., Weiss, D.S., Gartner, P., Linder, D. and Thauer, R.K. The energy conserving N5-methyltetrahydromethanopterin:coenzyme M methyltransferase complex from Methanobacterium thermoautotrophicum is composed of eight different subunits. Eur. J. Biochem. 228 (1995) 640–648. [PMID: 7737157]
5.  Gottschalk, G. and Thauer, R.K. The Na(+)-translocating methyltransferase complex from methanogenic archaea. Biochim. Biophys. Acta 1505 (2001) 28–36. [PMID: 11248186]
6.  Vepachedu, V.R. and Ferry, J.G. Role of the fused corrinoid/methyl transfer protein CmtA during CO-dependent growth of Methanosarcina acetivorans. J. Bacteriol. 194 (2012) 4161–4168. [PMID: 22636775]
[EC 2.1.1.86 created 1989, modified 2000, modified 2017]
 
 
EC 2.1.1.87     
Accepted name: pyridine N-methyltransferase
Reaction: S-adenosyl-L-methionine + pyridine = S-adenosyl-L-homocysteine + N-methylpyridinium
Other name(s): pyridine methyltransferase
Systematic name: S-adenosyl-L-methionine:pyridine N-methyltransferase
References:
1.  Damani, L.A., Shaker, M.S., Crooks, P.A., Godin, C.S. and Nwosu, C. N-Methylation and quaternization of pyridine in vitro by rabbit lung, liver and kidney N-methyltransferases: an S-adenosyl-L-methionine-dependent reaction. Xenobiotica 16 (1986) 645–650. [PMID: 3751119]
[EC 2.1.1.87 created 1989]
 
 
EC 2.1.1.88     
Accepted name: 8-hydroxyquercetin 8-O-methyltransferase
Reaction: S-adenosyl-L-methionine + 3,5,7,8,3′,4′-hexahydroxyflavone = S-adenosyl-L-homocysteine + 3,5,7,3′,4′-pentahydroxy-8-methoxyflavone
Other name(s): flavonol 8-O-methyltransferase; flavonol 8-methyltransferase; S-adenosyl-L-methionine:3,3′,4′,5,7,8-hexahydroxyflavone 8-O-methyltransferase; 8-hydroxyquercitin 8-O-methyltransferase [mis-spelt]
Systematic name: S-adenosyl-L-methionine:3,5,7,8,3′,4′-hexahydroxyflavone 8-O-methyltransferase
Comments: Also acts on 8-hydroxykaempferol, but not on the glycosides of 8-hydroxyflavonols. An enzyme from the flower buds of Lotus corniculatus.
References:
1.  Jay, M., De Luca, V. and Ibrahim, R.K. Purification, properties and kinetic mechanism of flavonol 8-O-methyltransferase from Lotus corniculatus L. Eur. J. Biochem. 153 (1985) 321–325. [PMID: 4076180]
[EC 2.1.1.88 created 1989]
 
 
EC 2.1.1.89     
Accepted name: tetrahydrocolumbamine 2-O-methyltransferase
Reaction: S-adenosyl-L-methionine + 5,8,13,13a-tetrahydrocolumbamine = S-adenosyl-L-homocysteine + tetrahydropalmatine
Other name(s): tetrahydrocolumbamine methyltransferase
Systematic name: S-adenosyl-L-methionine:5,8,13,13a-tetrahydrocolumbamine 2-O-methyltransferase
Comments: Involved in the biosynthesis of the berberine alkaloids.
References:
1.  Beecher, C.W.W. and Kelleher, W.J. Enzymatic study of the late stages of protoberberine alkaloid biosynthesis. Tetrahedron Lett. 25 (1984) 4595–4598.
[EC 2.1.1.89 created 1989]
 
 
EC 2.1.1.90     
Accepted name: methanol—corrinoid protein Co-methyltransferase
Reaction: methanol + a [Co(I) methanol-specific corrinoid protein] = a [methyl-Co(III) methanol-specific corrinoid protein] + H2O
Other name(s): methanol cobalamin methyltransferase; methanol:5-hydroxybenzimidazolylcobamide methyltransferase; MT 1 (ambiguous); methanol—5-hydroxybenzimidazolylcobamide Co-methyltransferase; mtaB (gene name)
Systematic name: methanol:5-hydroxybenzimidazolylcobamide Co-methyltransferase
Comments: The enzyme, which catalyses the transfer of methyl groups from methanol to a methanol-specific corrinoid protein (MtaC), is involved in methanogenesis from methanol. Methylation of the corrinoid protein requires the central cobalt to be in the Co(I) state. During methylation the cobalt is oxidized to the Co(III) state. Free cob(I)alamin can substitute for the corrinoid protein in vitro [2]. Inactivated by oxygen and other oxidizing agents, and reactivated by catalytic amounts of ATP and hydrogen.
References:
1.  van der Meijden, P., te Brömmelstroet, B.W., Poirot, C.M., van der Drift, C. and Vogels, G.D. Purification and properties of methanol:5-hydroxybenzimidazolylcobamide methyltransferase from Methanosarcina barkeri. J. Bacteriol. 160 (1984) 629–635. [PMID: 6438059]
2.  Sauer, K. and Thauer, R.K. Methanol:coenzyme M methyltransferase from Methanosarcina barkeri – substitution of the corrinoid harbouring subunit MtaC by free cob(I)alamin. Eur. J. Biochem. 261 (1999) 674–681. [PMID: 10215883]
[EC 2.1.1.90 created 1989, modified 2012]
 
 
EC 2.1.1.91     
Accepted name: isobutyraldoxime O-methyltransferase
Reaction: S-adenosyl-L-methionine + 2-methylpropanal oxime = S-adenosyl-L-homocysteine + 2-methylpropanal O-methyloxime
Other name(s): aldoxime methyltransferase; S-adenosylmethionine:aldoxime O-methyltransferase; aldoxime O-methyltransferase
Systematic name: S-adenosyl-L-methionine:2-methylpropanal-oxime O-methyltransferase
Comments: Oximes of C4 to C6 aldehydes can act as acceptors; the most active substrate is 2-methylbutyroaldoxime.
References:
1.  Harper, D.B. and Kennedy, J.T. Purification and properties of S-adenosylmethionine: aldoxime O-methyltransferase from Pseudomonas sp. N.C.I.B. 11652. Biochem. J. 226 (1985) 147–153. [PMID: 3977861]
[EC 2.1.1.91 created 1989]
 
 
EC 2.1.1.92      
Deleted entry: bergaptol O-methyltransferase. Now included with EC 2.1.1.69, 5-hydroxyfuranocoumarin 5-O-methyltransferase. The reaction with bergaptol is a specific example of the general reaction associated with EC 2.1.1.69
[EC 2.1.1.92 created 1989, deleted 2006]
 
 
EC 2.1.1.93      
Deleted entry: xanthotoxol O-methyltransferase. Enzyme is identical to EC 2.1.1.70, 8-hydroxyfuranocoumarin 8-O-methyltransferase
[EC 2.1.1.93 created 1989, deleted 2008]
 
 
EC 2.1.1.94     
Accepted name: tabersonine 16-O-methyltransferase
Reaction: S-adenosyl-L-methionine + 16-hydroxytabersonine = S-adenosyl-L-homocysteine + 16-methoxytabersonine
Other name(s): 11-demethyl-17-deacetylvindoline 11-methyltransferase; 11-O-demethyl-17-O-deacetylvindoline O-methyltransferase; S-adenosyl-L-methionine:11-O-demethyl-17-O-deacetylvindoline 11-O-methyltransferase
Systematic name: S-adenosyl-L-methionine:16-hydroxytabersonine 16-O-methyltransferase
Comments: Involved in the biosynthesis of vindoline from tabersonine in the Madagascar periwinkle, Catharanthus roseus.
References:
1.  De Luca, V., Balsevich, J., Tyler, R.T., Eilert, U., Panchuk, B.D. and Kurz, W.G.W. Biosynthesis of indole alkaloids - developmental regulation of the biosynthetic-pathway from tabersonine to vindoline in Catharanthus roseus. J. Plant Physiol. 125 (1986) 147–156.
2.  Fahn, W., Laussermair, E., Deus-Neumann, B. and Stöckigt, J. Late enzymes of vindoline biosynthesis. S-Adenosyl-L-methionine:11-O-demethyl-17-O-deacetylvindoline 11-O-methylase and unspecific acetylesterase. Plant Cell Rep. 4 (1985) 337–340. [PMID: 24254077]
[EC 2.1.1.94 created 1989, modified 2005]
 
 
EC 2.1.1.95     
Accepted name: tocopherol C-methyltransferase
Reaction: (1) S-adenosyl-L-methionine + γ-tocopherol = S-adenosyl-L-homocysteine + α-tocopherol
(2) S-adenosyl-L-methionine + δ-tocopherol = S-adenosyl-L-homocysteine + β-tocopherol
(3) S-adenosyl-L-methionine + γ-tocotrienol = S-adenosyl-L-homocysteine + α-tocotrienol
(4) S-adenosyl-L-methionine + δ-tocotrienol = S-adenosyl-L-homocysteine + β-tocotrienol
Other name(s): γ-tocopherol methyltransferase; VTE4 (gene name); S-adenosyl-L-methionine:γ-tocopherol 5-O-methyltransferase (incorrect); tocopherol O-methyltransferase (incorrect)
Systematic name: S-adenosyl-L-methionine:γ-tocopherol 5-C-methyltransferase
Comments: The enzymes from plants and photosynthetic bacteria have similar efficiency with the γ and δ isomers of tocopherols and tocotrienols.
References:
1.  Camara, B. and d'Harlingue, A. Demonstration and solubilization of S-adenosylmethionine: γ-tocopherol methyltransferase from Capsicum chromoplasts. Plant Cell Rep. 4 (1985) 31–32. [PMID: 24253640]
2.  Koch, M., Lemke, R., Heise, K.P. and Mock, H.P. Characterization of γ-tocopherol methyltransferases from Capsicum annuum L and Arabidopsis thaliana. Eur. J. Biochem. 270 (2003) 84–92. [PMID: 12492478]
3.  Zhang, G.Y., Liu, R.R., Xu, G., Zhang, P., Li, Y., Tang, K.X., Liang, G.H. and Liu, Q.Q. Increased α-tocotrienol content in seeds of transgenic rice overexpressing Arabidopsis γ-tocopherol methyltransferase. Transgenic Res. 22 (2013) 89–99. [PMID: 22763462]
[EC 2.1.1.95 created 1989, modified 2013, modified 2019]
 
 
EC 2.1.1.96     
Accepted name: thioether S-methyltransferase
Reaction: S-adenosyl-L-methionine + dimethyl sulfide = S-adenosyl-L-homocysteine + trimethylsulfonium
Other name(s): S-adenosyl-L-methionine:thioether S-methyltransferase; thioether methyltransferase
Systematic name: S-adenosyl-L-methionine:dimethyl-sulfide S-methyltransferase
Comments: Also acts on dimethyl selenide, dimethyl telluride, diethyl sulfide, 1,4-dithiane and many other thioethers.
References:
1.  Mozier, N.M., McConnell, P. and Hoffman, J.L. S-Adenosyl-L-methionine:thioether S-methyltransferase, a new enzyme in sulfur and selenium metabolism. J. Biol. Chem. 263 (1988) 4527–4531. [PMID: 3350800]
[EC 2.1.1.96 created 1990]
 
 
EC 2.1.1.97     
Accepted name: 3-hydroxyanthranilate 4-C-methyltransferase
Reaction: S-adenosyl-L-methionine + 3-hydroxyanthranilate = S-adenosyl-L-homocysteine + 3-hydroxy-4-methylanthranilate
Other name(s): 3-hydroxyanthranilate 4-methyltransferase
Systematic name: S-adenosyl-L-methionine:3-hydroxyanthranilate 4-C-methyltransferase
Comments: Involved in the biosynthesis of the antibiotic actinomycin in Streptomyces antibioticus.
References:
1.  Fawaz, F. and Jones, G.H. Actinomycin synthesis in Streptomyces antibioticus. Purification and properties of a 3-hydroxyanthranilate 4-methyltransferase. J. Biol. Chem. 263 (1988) 4602–4606. [PMID: 2450873]
[EC 2.1.1.97 created 1990]
 
 
EC 2.1.1.98     
Accepted name: diphthine synthase
Reaction: 3 S-adenosyl-L-methionine + 2-[(3S)-3-carboxy-3-aminopropyl]-L-histidine-[translation elongation factor 2] = 3 S-adenosyl-L-homocysteine + diphthine-[translation elongation factor 2] (overall reaction)
(1a) S-adenosyl-L-methionine + 2-[(3S)-3-carboxy-3-aminopropyl]-L-histidine-[translation elongation factor 2] = S-adenosyl-L-homocysteine + 2-[(3S)-3-carboxy-3-(methylamino)propyl]-L-histidine-[translation elongation factor 2]
(1b) S-adenosyl-L-methionine + 2-[(3S)-3-carboxy-3-(methylamino)propyl]-L-histidine-[translation elongation factor 2] = S-adenosyl-L-homocysteine + 2-[(3S)-3-carboxy-3-(dimethylamino)propyl]-L-histidine-[translation elongation factor 2]
(1c) S-adenosyl-L-methionine + 2-[(3S)-3-carboxy-3-(dimethylamino)propyl]-L-histidine-[translation elongation factor 2] = S-adenosyl-L-homocysteine + diphthine-[translation elongation factor 2]
Glossary: diphthine = 2-[(3S)-3-carboxy-3-(trimethylamino)propyl]-L-histidine
Other name(s): S-adenosyl-L-methionine:elongation factor 2 methyltransferase (ambiguous); diphthine methyltransferase (ambiguous); S-adenosyl-L-methionine:2-(3-carboxy-3-aminopropyl)-L-histidine-[translation elongation factor 2] methyltransferase; Dph5 (ambiguous)
Systematic name: S-adenosyl-L-methionine:2-[(3S)-3-carboxy-3-aminopropyl]-L-histidine-[translation elongation factor 2] methyltransferase (diphthine-[translation elongation factor 2]-forming)
Comments: This archaeal enzyme produces the trimethylated product diphthine, which is converted into diphthamide by EC 6.3.1.14, diphthine—ammonia ligase. Different from the eukaryotic enzyme, which produces diphthine methyl ester (cf. EC 2.1.1.314). In the archaeon Pyrococcus horikoshii the enzyme acts on His600 of elongation factor 2.
References:
1.  Zhu, X., Kim, J., Su, X. and Lin, H. Reconstitution of diphthine synthase activity in vitro. Biochemistry 49 (2010) 9649–9657. [PMID: 20873788]
[EC 2.1.1.98 created 1990, modified 2013, modified 2015]
 
 
EC 2.1.1.99     
Accepted name: 3-hydroxy-16-methoxy-2,3-dihydrotabersonine N-methyltransferase
Reaction: S-adenosyl-L-methionine + 3-hydroxy-16-methoxy-2,3-dihydrotabersonine = S-adenosyl-L-homocysteine + deacetoxyvindoline
Other name(s): 16-methoxy-2,3-dihydro-3-hydroxytabersonine methyltransferase; NMT; 16-methoxy-2,3-dihydro-3-hydroxytabersonine N-methyltransferase; S-adenosyl-L-methionine:16-methoxy-2,3-dihydro-3-hydroxytabersonine N-methyltransferase
Systematic name: S-adenosyl-L-methionine:3-hydroxy-16-methoxy-2,3-dihydrotabersonine N-methyltransferase
Comments: Involved in the biosynthesis of vindoline from tabersonine in the Madagascar periwinkle Catharanthus roseus.
References:
1.  De Luca, V., Balsevich, J., Tyler, R.T., Eilert, U., Panchuk, B.D. and Kurz, W.G.W. Biosynthesis of indole alkaloids - developmental regulation of the biosynthetic-pathway from tabersonine to vindoline in Catharanthus roseus. J. Plant Physiol. 125 (1986) 147–156.
2.  De Luca, V. and Cutler, A.J. Subcellular localization of enzymes involved in indole alkaloid biosynthesis in Catharanthus roseus. Plant Physiol. 85 (1987) 1099–1102. [PMID: 16665811]
[EC 2.1.1.99 created 1990, modified 2005]
 
 
EC 2.1.1.100     
Accepted name: protein-S-isoprenylcysteine O-methyltransferase
Reaction: S-adenosyl-L-methionine + protein C-terminal S-farnesyl-L-cysteine = S-adenosyl-L-homocysteine + protein C-terminal S-farnesyl-L-cysteine methyl ester
Other name(s): farnesyl cysteine C-terminal methyltransferase; farnesyl-protein carboxymethyltransferase; protein C-terminal farnesylcysteine O-methyltransferase; farnesylated protein C-terminal O-methyltransferase; isoprenylated protein methyltransferase; prenylated protein methyltransferase; protein S-farnesylcysteine C-terminal methyltransferase; S-farnesylcysteine methyltransferase; prenylcysteine carboxylmethyltransferase [misleading]; prenylcysteine carboxymethyltransferase [misleading]; prenylcysteine methyltransferase
Systematic name: S-adenosyl-L-methionine:protein-C-terminal-S-farnesyl-L-cysteine O-methyltransferase
Comments: C-terminal S-geranylgeranylcysteine and S-geranylcysteine residues are also methylated, but more slowly.
References:
1.  Clarke, S., Vogel, J.P., Deschenes, R.J. and Stock, J. Posttranslational modification of the Ha-ras oncogene protein: evidence for a third class of protein carboxyl methyltransferases. Proc. Natl. Acad. Sci. USA 85 (1988) 4643–4647. [PMID: 3290900]
2.  Ota, I.M. and Clarke, S. Enzymatic methylation of 23-29-kDa bovine retinal rod outer segment membrane proteins. Evidence for methyl ester formation at carboxyl-terminal cysteinyl residues. J. Biol. Chem. 264 (1989) 12879–12884. [PMID: 2753892]
3.  Stephenson, R.C. and Clarke, S. Identification of a C-terminal protein carboxyl methyltransferase in rat liver membranes utilizing a synthetic farnesyl cysteine-containing peptide substrate. J. Biol. Chem. 265 (1990) 16248–16254. [PMID: 2398053]
[EC 2.1.1.100 created 1992 (EC 2.1.1.24 created 1972, modified 1983, modified 1989, part incorporated 1992)]
 
 
EC 2.1.1.101     
Accepted name: macrocin O-methyltransferase
Reaction: S-adenosyl-L-methionine + macrocin = S-adenosyl-L-homocysteine + tylosin
Other name(s): macrocin methyltransferase; S-adenosyl-L-methionine-macrocin O-methyltransferase; MOMT (ambiguous); tylF (gene name)
Systematic name: S-adenosyl-L-methionine:macrocin 3′′′-O-methyltransferase
Comments: Requires Mg2+, Mn2+ or Co2+. The 3-hydroxy group of the 2-O-methyl-6-deoxy-D-allose moiety in the macrolide antibiotic macrosin acts as methyl acceptor, generating tylosin, another macrolide antibiotic. Isolated from the bacterium Streptomyces fradiae. Not identical with EC 2.1.1.102, demethylmacrocin O-methyltransferase.
References:
1.  Bauer, N.J., Kreuzman, A.J., Dotzlaf, J.E. and Yeh, W.-K. Purification, characterization, and kinetic mechanism of S-adenosyl-L-methionine:macrocin O-methyltransferase from Streptomyces fradiae. J. Biol. Chem. 263 (1988) 15619–15625. [PMID: 3170601]
2.  Kreuzman, A.J., Turner, J.R. and Yeh, W.-K. Two distinctive O-methyltransferases catalyzing penultimate and terminal reactions of macrolide antibiotic (tylosin) biosynthesis. Substrate specificity, enzyme inhibition, and kinetic mechanism. J. Biol. Chem. 263 (1988) 15626–15633. [PMID: 3170602]
[EC 2.1.1.101 created 1992]
 
 
EC 2.1.1.102     
Accepted name: demethylmacrocin O-methyltransferase
Reaction: S-adenosyl-L-methionine + demethylmacrocin = S-adenosyl-L-homocysteine + macrocin
Other name(s): demethylmacrocin methyltransferase; DMOMT
Systematic name: S-adenosyl-L-methionine:demethylmacrocin 2′′′-O-methyltransferase
Comments: Requires Mg2+. The enzyme, isolated from the bacterium Streptomyces fradiae, is involved in the biosynthesis of the macrolide antibiotic tylosin. The 2-hydroxy group of a 6-deoxy-D-allose moiety in demethylmacrocin acts as the methyl acceptor. Also acts on demethyllactenocin, giving lactenocin. Not identical with EC 2.1.1.101 macrocin O-methyltransferase.
References:
1.  Kreuzman, A.J., Turner, J.R. and Yeh, W.-K. Two distinctive O-methyltransferases catalyzing penultimate and terminal reactions of macrolide antibiotic (tylosin) biosynthesis. Substrate specificity, enzyme inhibition, and kinetic mechanism. J. Biol. Chem. 263 (1988) 15626–15633. [PMID: 3170602]
[EC 2.1.1.102 created 1992]
 
 
EC 2.1.1.103     
Accepted name: phosphoethanolamine N-methyltransferase
Reaction: S-adenosyl-L-methionine + ethanolamine phosphate = S-adenosyl-L-homocysteine + N-methylethanolamine phosphate
Other name(s): phosphoethanolamine methyltransferase
Systematic name: S-adenosyl-L-methionine:ethanolamine-phosphate N-methyltransferase
Comments: The enzyme may catalyse the transfer of two further methyl groups to the product.
References:
1.  Datko, A.H. and Mudd, S.H. Enzymes of phosphatidylcholine synthesis in Lemna, soybean, and carrot. Plant Physiol. 88 (1988) 1338–1348. [PMID: 16666464]
[EC 2.1.1.103 created 1992]
 
 
EC 2.1.1.104     
Accepted name: caffeoyl-CoA O-methyltransferase
Reaction: S-adenosyl-L-methionine + caffeoyl-CoA = S-adenosyl-L-homocysteine + feruloyl-CoA
Other name(s): caffeoyl coenzyme A methyltransferase; caffeoyl-CoA 3-O-methyltransferase; trans-caffeoyl-CoA 3-O-methyltransferase
Systematic name: S-adenosyl-L-methionine:caffeoyl-CoA 3-O-methyltransferase
References:
1.  Kühnl, T., Koch, U., Heller, W. and Wellmann, E. Elicitor induced S-adenosyl-L-methionine - caffeoyl-CoA 3-O-methyltransferase from carrot cell-suspension cultures. Plant Sci. 60 (1989) 21–25.
[EC 2.1.1.104 created 1992]
 
 
EC 2.1.1.105     
Accepted name: N-benzoyl-4-hydroxyanthranilate 4-O-methyltransferase
Reaction: S-adenosyl-L-methionine + N-benzoyl-4-hydroxyanthranilate = S-adenosyl-L-homocysteine + N-benzoyl-4-methoxyanthranilate
Other name(s): N-benzoyl-4-hydroxyanthranilate 4-methyltransferase; benzoyl-CoA:anthranilate N-benzoyltransferase
Systematic name: S-adenosyl-L-methionine:N-benzoyl-4-O-hydroxyanthranilate 4-O-methyltransferase
Comments: Involved in the biosynthesis of phytoalexins.
References:
1.  Reinhard, K. and Matern, U. The biosynthesis of phytoalexins in Dianthus caryophyllus L. cell cultures: induction of benzoyl-CoA:anthranilate N-benzoyltransferase activity. Arch. Biochem. Biophys. 275 (1989) 295–301. [PMID: 2817901]
[EC 2.1.1.105 created 1992]
 
 
EC 2.1.1.106     
Accepted name: tryptophan 2-C-methyltransferase
Reaction: S-adenosyl-L-methionine + L-tryptophan = S-adenosyl-L-homocysteine + L-2-methyltryptophan
Other name(s): tsrM (gene name); tryptophan 2-methyltransferase; S-adenosylmethionine:tryptophan 2-methyltransferase
Systematic name: S-adenosyl-L-methionine:L-tryptophan 2-C-methyltransferase
Comments: The enzyme, characterized from the bacterium Streptomyces laurentii, is involved in thiostrepton biosynthesis. It is a radical SAM enzyme that contains a [4Fe-4S] center and a cobalamin cofactor. The enzyme first transfers the methyl group from SAM to the bound cobalamin, followed by transfer from methylcobalamin to L-tryptophan, resulting in retention of the original methyl group configuration. The second transfer is likely to involve a CH3 radical species formed from methylcobalamin by the concerted action of a partially ligated radical SAM [4Fe-4S]2+/1+ center.
References:
1.  Frenzel, T., Zhou, P. and Floss, H.G. Formation of 2-methyltryptophan in the biosynthesis of thiostrepton: isolation of S-adenosylmethionine:tryptophan 2-methyltransferase. Arch. Biochem. Biophys. 278 (1990) 35–40. [PMID: 2321967]
2.  Pierre, S., Guillot, A., Benjdia, A., Sandstrom, C., Langella, P. and Berteau, O. Thiostrepton tryptophan methyltransferase expands the chemistry of radical SAM enzymes. Nat. Chem. Biol. 8 (2012) 957–959. [PMID: 23064318]
3.  Blaszczyk, A.J., Silakov, A., Zhang, B., Maiocco, S.J., Lanz, N.D., Kelly, W.L., Elliott, S.J., Krebs, C. and Booker, S.J. Spectroscopic and Electrochemical Characterization of the Iron-Sulfur and Cobalamin Cofactors of TsrM, an Unusual Radical S-Adenosylmethionine Methylase. J. Am. Chem. Soc. 138 (2016) 3416–3426. [PMID: 26841310]
4.  Blaszczyk, A.J., Wang, B., Silakov, A., Ho, J.V. and Booker, S.J. Efficient methylation of C2 in L-tryptophan by the cobalamin-dependent radical S-adenosylmethionine methylase TsrM requires an unmodified N1 amine. J. Biol. Chem. 292 (2017) 15456–15467. [PMID: 28747433]
[EC 2.1.1.106 created 1992]
 
 
EC 2.1.1.107     
Accepted name: uroporphyrinogen-III C-methyltransferase
Reaction: 2 S-adenosyl-L-methionine + uroporphyrinogen III = 2 S-adenosyl-L-homocysteine + precorrin-2 (overall reaction)
(1a) S-adenosyl-L-methionine + uroporphyrinogen III = S-adenosyl-L-homocysteine + precorrin-1
(1b) S-adenosyl-L-methionine + precorrin-1 = S-adenosyl-L-homocysteine + precorrin-2
Glossary: uroprphyrinogen-III = 5,10,15,20,22,24-hexahydrouroporphyrin-III
Other name(s): uroporphyrinogen methyltransferase; uroporphyrinogen-III methyltransferase; adenosylmethionine-uroporphyrinogen III methyltransferase; S-adenosyl-L-methionine-dependent uroporphyrinogen III methylase; uroporphyrinogen-III methylase; SirA; CysG; CobA [ambiguous - see EC 2.5.1.17] SUMT; uroporphyrin-III C-methyltransferase (incorrect); S-adenosyl-L-methionine:uroporphyrin-III C-methyltransferase (incorrect)
Systematic name: S-adenosyl-L-methionine:uroporphyrinogen-III C-methyltransferase
Comments: This enzyme catalyses two sequential methylation reactions, the first forming precorrin-1 and the second leading to the formation of precorrin-2. It is the first of three steps leading to the formation of siroheme from uroporphyrinogen III. The second step involves an NAD+-dependent dehydrogenation to form sirohydrochlorin from precorrin-2 (EC 1.3.1.76, precorrin-2 dehydrogenase) and the third step involves the chelation of Fe2+ to sirohydrochlorin to form siroheme (EC 4.99.1.4, sirohydrochlorin ferrochelatase). In Saccharomyces cerevisiae, the last two steps are carried out by a single bifunctional enzyme, Met8p. In some bacteria, steps 1-3 are catalysed by a single multifunctional protein called CysG, whereas in Bacillus megaterium, three separate enzymes carry out each of the steps, with SirA being responsible for the above reaction. Also involved in the biosynthesis of cobalamin.
References:
1.  Warren, M.J., Gonzalez, M.D., Williams, H.J., Stolowich, N.J. and Scott, A.I. Uroporphyrinogen-III methylase catalyzes the enzymatic-synthesis of sirohydrochlorin-II and sirohydrochlorin-IV by a clockwise mechanism. J. Am. Chem. Soc. 112 (1990) 5343–5345.
2.  Warren, M.J., Roessner, C.A., Santander, P.J. and Scott, A.I. The Escherichia coli cysG gene encodes S-adenosylmethionine-dependent uroporphyrinogen III methylase. Biochem. J. 265 (1990) 725–729. [PMID: 2407234]
3.  Schubert, H.L., Raux, E., Brindley, A.A., Leech, H.K., Wilson, K.S., Hill, C.P. and Warren, M.J. The structure of Saccharomyces cerevisiae Met8p, a bifunctional dehydrogenase and ferrochelatase. EMBO J. 21 (2002) 2068–2075. [PMID: 11980703]
[EC 2.1.1.107 created 1992, modified 2004]
 
 
EC 2.1.1.108     
Accepted name: 6-hydroxymellein O-methyltransferase
Reaction: S-adenosyl-L-methionine + 6-hydroxymellein = S-adenosyl-L-homocysteine + 6-methoxymellein
Other name(s): 6-hydroxymellein methyltransferase
Systematic name: S-adenosyl-L-methionine:6-hydroxymellein 6-O-methyltransferase
Comments: 3,4-Dehydro-6-hydroxymellein can also act as acceptor. 6-Methoxymellein is a phytoalexin produced by carrot tissue.
References:
1.  Kurosaki, F. and Nishi, A. A methyltransferase for synthesis of the phytoalexin 6-methoxymellein in carrot cells. FEBS Lett. 227 (1988) 183–186.
[EC 2.1.1.108 created 1992]
 
 
EC 2.1.1.109     
Accepted name: demethylsterigmatocystin 6-O-methyltransferase
Reaction: S-adenosyl-L-methionine + 6-demethylsterigmatocystin = S-adenosyl-L-homocysteine + sterigmatocystin
Other name(s): demethylsterigmatocystin methyltransferase; O-methyltransferase I
Systematic name: S-adenosyl-L-methionine:6-demethylsterigmatocystin 6-O-methyltransferase
Comments: Dihydrodemethylsterigmatocystin can also act as acceptor. Involved in the biosynthesis of aflatoxins in fungi.
References:
1.  Yabe, K., Ando, Y., Hashimoto, J. and Hamasaki, T. 2 distinct O-methyltransferases in aflatoxin biosynthesis. Appl. Environ. Microbiol. 55 (1989) 2172–2177. [PMID: 2802602]
[EC 2.1.1.109 created 1992]
 
 
EC 2.1.1.110     
Accepted name: sterigmatocystin 8-O-methyltransferase
Reaction: (1) S-adenosyl-L-methionine + sterigmatocystin = S-adenosyl-L-homocysteine + 8-O-methylsterigmatocystin
(2) S-adenosyl-L-methionine + dihydrosterigmatocystin = S-adenosyl-L-homocysteine + 8-O-methyldihydrosterigmatocystin
Glossary: sterigmatocystin = 3a,12c-dihydro-8-hydroxy-6-methoxyfuro[3′,2′:4,5]furo[2,3-c]xanthen-7-one
dihydrosterigmatocystin = 1,2,3a,12c-tetrahydro-8-hydroxy-6-methoxyfuro[3′,2′:4,5]furo[2,3-c]xanthen-7-one
8-O-methylsterigmatocystin = 6,8-dimethoxy-3a,12c-dihydrofuro[3′,2′:4,5]furo[2,3-c]xanthen-7-one
8-O-methyldihydrosterigmatocystin = 6,8-dimethoxy-1,2,3a,12c-tetrahydrofuro[3′,2′:4,5]furo[2,3-c]xanthen-7-one
Other name(s): sterigmatocystin methyltransferase; O-methyltransferase II; sterigmatocystin 7-O-methyltransferase (incorrect); S-adenosyl-L-methionine:sterigmatocystin 7-O-methyltransferase (incorrect); OmtA
Systematic name: S-adenosyl-L-methionine:sterigmatocystin 8-O-methyltransferase
Comments: Dihydrosterigmatocystin can also act as acceptor. Involved in the biosynthesis of aflatoxins in fungi.
References:
1.  Bhatnagar, D., McCormick, S.P., Lee, L.S. and Hill, R.A. Identification of O-methylsterigmatocystin as an aflatoxin B1 and G1 precursor in Aspergillus parasiticus. Appl. Environ. Microbiol. 53 (1987) 1028–1033. [PMID: 3111363]
2.  Yabe, K., Ando, Y., Hashimoto, J. and Hamasaki, T. 2 distinct O-methyltransferases in aflatoxin biosynthesis. Appl. Environ. Microbiol. 55 (1989) 2172–2177. [PMID: 2802602]
3.  Yu, J., Cary, J.W., Bhatnagar, D., Cleveland, T.E., Keller, N.P. and Chu, F.S. Cloning and characterization of a cDNA from Aspergillus parasiticus encoding an O-methyltransferase involved in aflatoxin biosynthesis. Appl. Environ. Microbiol. 59 (1993) 3564–3571. [PMID: 8285664]
4.  Lee, L.W., Chiou, C.H. and Linz, J.E. Function of native OmtA in vivo and expression and distribution of this protein in colonies of Aspergillus parasiticus. Appl. Environ. Microbiol. 68 (2002) 5718–5727. [PMID: 12406770]
[EC 2.1.1.110 created 1992, modified 2005, modified 2013]
 
 
EC 2.1.1.111     
Accepted name: anthranilate N-methyltransferase
Reaction: S-adenosyl-L-methionine + anthranilate = S-adenosyl-L-homocysteine + N-methylanthranilate
Other name(s): anthranilic acid N-methyltransferase
Systematic name: S-adenosyl-L-methionine:anthranilate N-methyltransferase
Comments: Involved in the biosynthesis of acridine alkaloids in plant tissues.
References:
1.  Eilert, U. and Wolters, B. Elicitor induction of S-adenosyl-L-methionine-anthranilic acid N-methyltransferase activity in cell-suspension and organ-cultures of Ruta graveolens L. Plant Cell, Tissue Organ Cult. 18 (1989) 1–18.
[EC 2.1.1.111 created 1992]
 
 
EC 2.1.1.112     
Accepted name: glucuronoxylan 4-O-methyltransferase
Reaction: S-adenosyl-L-methionine + glucuronoxylan D-glucuronate = S-adenosyl-L-homocysteine + glucuronoxylan 4-O-methyl-D-glucuronate
Systematic name: S-adenosyl-L-methionine:glucuronoxylan-D-glucuronate 4-O-methyltransferase
References:
1.  Baydoun, E.A.-H., Usta, J.A.-R., Waldron, K.W. and Brett, C.T. A methyltransferase involved in the biosynthesis of 4-O-methylglucuronoxylan in etiolated pea epicotyls. J. Plant Physiol. 135 (1989) 81–85.
[EC 2.1.1.112 created 1992]
 
 
EC 2.1.1.113     
Accepted name: site-specific DNA-methyltransferase (cytosine-N4-specific)
Reaction: S-adenosyl-L-methionine + DNA cytosine = S-adenosyl-L-homocysteine + DNA N4-methylcytosine
Other name(s): modification methylase; restriction-modification system; DNA[cytosine-N4]methyltransferase; m4C-forming MTase; S-adenosyl-L-methionine:DNA-cytosine 4-N-methyltransferase
Systematic name: S-adenosyl-L-methionine:DNA-cytosine N4-methyltransferase
Comments: This is a large group of enzymes, most of which, with enzymes of similar site specificity listed as EC 3.1.21.3 (type 1 site-specific deoxyribonuclease), EC 3.1.21.4 (type II site-specific deoxyribonuclease) or EC 3.1.21.5 (type III site-specific deoxyribonuclease), form so-called ’restriction-modification systems’. A complete listing of all of these enzymes has been produced by R.J. Roberts and is available on-line at http://rebase.neb.com/rebase/rebase.html.
References:
1.  Kessler, C. and Manta, V. Specificity of restriction endonucleases and DNA modification methyltransferases: a review. Gene 92 (1990) 1–248. [PMID: 2172084]
2.  Klimasauskas, S., Timinskas, A., Menkevicius, S., Butkiene, D., Butkus, V. and Janulaitis, A. Sequence motifs characteristic of DNA[cytosine-N4]methyltransferases: similarity to adenine and cytosine-C5 DNA-methylases. Nucleic Acids Res. 17 (1989) 9823–9832. [PMID: 2690010]
3.  Roberts, R.J. Restriction enzymes and their isoschizomers. Nucleic Acids Res. 18 (1990) 2331–2365. [PMID: 2159140]
4.  Yuan, R. Structure and mechanism of multifunctional restriction endonucleases. Annu. Rev. Biochem. 50 (1981) 285–319. [PMID: 6267988]
[EC 2.1.1.113 created 1992]
 
 
EC 2.1.1.114     
Accepted name: polyprenyldihydroxybenzoate methyltransferase
Reaction: S-adenosyl-L-methionine + 3,4-dihydroxy-5-all-trans-polyprenylbenzoate = S-adenosyl-L-homocysteine + 3-methoxy-4-hydroxy-5-all-trans-polyprenylbenzoate
Other name(s): 3,4-dihydroxy-5-hexaprenylbenzoate methyltransferase; dihydroxyhexaprenylbenzoate methyltransferase; COQ3 (gene name); Coq3 O-methyltransferase; DHHB O-methyltransferase
Systematic name: S-adenosyl-L-methionine:3,4-dihydroxy-5-all-trans-polyprenylbenzoate 3-O-methyltransferase
Comments: This enzyme is involved in ubiquinone biosynthesis. Ubiquinones from different organisms have a different number of prenyl units (for example, ubiquinone-6 in Saccharomyces, ubiquinone-9 in rat and ubiquinone-10 in human), and thus the natural substrate for the enzymes from different organisms has a different number of prenyl units. However, the enzyme usually shows a low degree of specificity regarding the number of prenyl units. For example, the human COQ3 enzyme can restore biosynthesis of ubiquinone-6 in coq3 deletion mutants of yeast [3]. The enzymes from yeast and rat also catalyse the methylation of 3-demethylubiquinol-6 and 3-demethylubiquinol-9, respectively [2] (this activity is classified as EC 2.1.1.64, 3-demethylubiquinol 3-O-methyltransferase).
References:
1.  Clarke, C.F., Williams, W., Teruya, J.H. Ubiquinone biosynthesis in Saccharomyces cerevisiae. Isolation and sequence of COQ3, the 3,4-dihydroxy-5-hexaprenylbenzoate methyltransferase gene. J. Biol. Chem. 266 (1991) 16636–16641. [PMID: 1885593]
2.  Poon, W.W., Barkovich, R.J., Hsu, A.Y., Frankel, A., Lee, P.T., Shepherd, J.N., Myles, D.C. and Clarke, C.F. Yeast and rat Coq3 and Escherichia coli UbiG polypeptides catalyze both O-methyltransferase steps in coenzyme Q biosynthesis. J. Biol. Chem. 274 (1999) 21665–21672. [PMID: 10419476]
3.  Jonassen, T. and Clarke, C.F. Isolation and functional expression of human COQ3, a gene encoding a methyltransferase required for ubiquinone biosynthesis. J. Biol. Chem. 275 (2000) 12381–12387. [PMID: 10777520]
4.  Xing, L., Zhu, Y., Fang, P., Wang, J., Zeng, F., Li, X., Teng, M. and Li, X. Crystallization and preliminary crystallographic studies of UbiG, an O-methyltransferase from Escherichia coli. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 67 (2011) 727–729. [PMID: 21636923]
[EC 2.1.1.114 created 1999]
 
 
EC 2.1.1.115     
Accepted name: (RS)-1-benzyl-1,2,3,4-tetrahydroisoquinoline N-methyltransferase
Reaction: S-adenosyl-L-methionine + (RS)-1-benzyl-1,2,3,4-tetrahydroisoquinoline = S-adenosyl-L-homocysteine + N-methyl-(RS)-1-benzyl-1,2,3,4-tetrahydroisoquinoline
Other name(s): norreticuline N-methyltransferase
Systematic name: S-adenosyl-L-methionine:(RS)-1-benzyl-1,2,3,4-tetrahydroisoquinoline N-methyltransferase
Comments: Broad substrate specificity for (RS)-1-benzyl-1,2,3,4-tetrahydroisoquinolines; including coclaurine, norcoclaurine, isococlaurine, norarmepavine, norreticuline and tetrahydropapaverine. Both R- and S-enantiomers are methylated. The enzyme participates in the pathway leading to benzylisoquinoline alkaloid synthesis in plants. The physiological substrate is likely to be coclaurine. The enzyme was earlier termed norreticuline N-methyltransferase. However, norreticuline has not been found to occur in nature and that name does not reflect the broad specificity of the enzyme for (RS)-1-benzyl-1,2,3,4-tetrahydroisoquinolines.
References:
1.  Frenzel, T., Zenk, M.H. Purification and characterization of three isoforms of S-adenosyl-L-methionine: (R,S)-tetrahydrobenzyl-isoquinoline N-methyltransferase from Berberis koetineana cell cultures. Phytochemistry 29 (1990) 3491–3497.
[EC 2.1.1.115 created 1999]
 
 
EC 2.1.1.116     
Accepted name: 3′-hydroxy-N-methyl-(S)-coclaurine 4′-O-methyltransferase
Reaction: S-adenosyl-L-methionine + 3′-hydroxy-N-methyl-(S)-coclaurine = S-adenosyl-L-homocysteine + (S)-reticuline
Systematic name: S-adenosyl-L-methionine:3′-hydroxy-N-methyl-(S)-coclaurine 4′-O-methyltransferase
Comments: Involved in isoquinoline alkaloid metabolism in plants. The enzyme has also been shown to catalyse the methylation of (RS)-laudanosoline, (S)-3′-hydroxycoclaurine and (RS)-7-O-methylnorlaudanosoline.
References:
1.  Frenzel, T., Zenk, M.H. S-Adenosyl-L-methionine: 3′-hydroxy-N-methyl-(S)-coclaurine 4′-O-methyltransferase, a regio- and stereoselective enzyme of the (S)-reticuline pathway. Phytochemistry 29 (1990) 3505–3511.
[EC 2.1.1.116 created 1999]
 
 
EC 2.1.1.117     
Accepted name: (S)-scoulerine 9-O-methyltransferase
Reaction: S-adenosyl-L-methionine + (S)-scoulerine = S-adenosyl-L-homocysteine + (S)-tetrahydrocolumbamine
Systematic name: S-adenosyl-L-methionine:(S)-scoulerine 9-O-methyltransferase
Comments: The product of this reaction is a precursor for protoberberine alkaloids in plants
References:
1.  Muemmler, S., Rueffer, M., Nagakura, N., Zenk, M.H. S-Adenosyl-L-methionine:(S)-scoulerine 9-O-methyltransferase, a highly stereo- and regiospecific enzyme in tetrahydroberberine biosynthesis. Plant Cell Reports 4 (1985) 36–39. [PMID: 24253642]
[EC 2.1.1.117 created 1999]
 
 
EC 2.1.1.118     
Accepted name: columbamine O-methyltransferase
Reaction: S-adenosyl-L-methionine + columbamine = S-adenosyl-L-homocysteine + palmatine
Systematic name: S-adenosyl-L-methionine:columbamine O-methyltransferase
Comments: The product of this reaction is a protoberberine alkaloid that is widely distributed in the plant kingdom. This enzyme is distinct in specificity from EC 2.1.1.88, 8-hydroxyquercetin 8-O-methyltransferase.
References:
1.  Rueffer, M., Amann, M., Zenk, M.H. S-Adenosyl-L-methionine:columbamine O-methyltransferase, a compartmentalized enzyme in protoberberine biosynthesis. Plant Cell Reports 3 (1986) 182–185.
[EC 2.1.1.118 created 1999]
 
 
EC 2.1.1.119     
Accepted name: 10-hydroxydihydrosanguinarine 10-O-methyltransferase
Reaction: S-adenosyl-L-methionine + 10-hydroxydihydrosanguinarine = S-adenosyl-L-homocysteine + dihydrochelirubine
Systematic name: S-adenosyl-L-methionine:10-hydroxydihydrosanguinarine 10-O-methyltransferase
Comments: This reaction is part of the pathway for synthesis of benzophenanthridine alkaloids in plants.
References:
1.  De-Eknamkul, W., Tanahashi, T. and Zenk, M.H. Enzymic 10-hydroxylation and 10-O-methylation of dihydrosanguinarine in dihydrochelirubine formation by Eschscholtzia. Phytochemistry 31 (1992) 2713–2717.
[EC 2.1.1.119 created 1999]
 
 
EC 2.1.1.120     
Accepted name: 12-hydroxydihydrochelirubine 12-O-methyltransferase
Reaction: S-adenosyl-L-methionine + 12-hydroxydihydrochelirubine = S-adenosyl-L-homocysteine + dihydromacarpine
Systematic name: S-adenosyl-L-methionine:12-hydroxydihydrochelirubine 12-O-methyltransferase
Comments: This reaction is part of the pathway for synthesis of benzophenanthridine alkaloid macarpine in plants.
References:
1.  Kammerer, L., De-Eknamkul, W. and Zenk, M.H. Enzymic 12-hydroxylation and 12-O-methylation of dihydrochelirubine in dihydromacarpine formation by Thalictrum bulgaricum. Phytochemistry 36 (1994) 1409–1416.
[EC 2.1.1.120 created 1999]
 
 
EC 2.1.1.121     
Accepted name: 6-O-methylnorlaudanosoline 5′-O-methyltransferase
Reaction: S-adenosyl-L-methionine + 6-O-methylnorlaudanosoline = S-adenosyl-L-homocysteine + nororientaline
Systematic name: S-adenosyl-L-methionine:6-O-methylnorlaudanosoline 5′-O-methyltransferase
Comments: Nororientaline is a precursor of the alkaloid papaverine.
References:
1.  Rueffer, M., Nagakura, N., Zenk, M.H. A highly specific O-methyltransferase for nororientaline synthesis isolated from Argemone platyceras cell cultures. Planta Med. 49 (1983) 196–198. [PMID: 17405051]
[EC 2.1.1.121 created 1999]
 
 
EC 2.1.1.122     
Accepted name: (S)-tetrahydroprotoberberine N-methyltransferase
Reaction: S-adenosyl-L-methionine + (S)-7,8,13,14-tetrahydroprotoberberine = S-adenosyl-L-homocysteine + cis-N-methyl-(S)-7,8,13,14-tetrahydroprotoberberine
Other name(s): tetrahydroprotoberberine cis-N-methyltransferase
Systematic name: S-adenosyl-L-methionine:(S)-7,8,13,14-tetrahydroprotoberberine cis-N-methyltransferase
Comments: Involved in the biosynthesis of isoquinoline alkaloids in plants.
References:
1.  Rueffer, M., Zumstein, G., Zenk, M.H. Partial purification and characterization of S-adenosyl-L-methionine:(S)-tetrahydroprotoberberine cis-N-methyltransferase from suspension-cultured cells of Eschscholtzia and Corydalis. Phytochemistry 29 (1990) 3727–3733.
[EC 2.1.1.122 created 1999]
 
 
EC 2.1.1.123     
Accepted name: [cytochrome-c]-methionine S-methyltransferase
Reaction: S-adenosyl-L-methionine + [cytochrome c]-methionine = S-adenosyl-L-homocysteine + [cytochrome c]-S-methyl-methionine
Systematic name: S-adenosyl-L-methionine:[cytochrome c]-methionine S-methyltransferase
Comments: The enzyme from Euglena gracilis methylates Met-65 of horse heart cytochrome c.
References:
1.  Farooqui, J.Z., Tuck, M., Paik, W.K. Purification and characterization of enzymes from Euglena gracilis that methylate methionine and arginine residues of cytochrome c. J. Biol. Chem. 260 (1985) 537–545. [PMID: 2981218]
[EC 2.1.1.123 created 1999]
 
 
EC 2.1.1.124      
Deleted entry: [cytochrome c]-arginine N-methyltransferase. Now covered by EC 2.1.1.319, type I protein arginine methyltransferase, EC 2.1.1.320, type II protein arginine methyltransferase, EC 2.1.1.321, type III protein arginine methyltransferase and EC 2.1.1.322, type IV protein arginine methyltransferase
[EC 2.1.1.124 created 1999 (EC 2.1.1.23 created 1972, modified 1976, modified 1983, part incorporated 1999), deleted 2015]
 
 
EC 2.1.1.125      
Deleted entry: histone-arginine N-methyltransferase. Now covered by EC 2.1.1.319, type I protein arginine methyltransferase, EC 2.1.1.320, type II protein arginine methyltransferase, EC 2.1.1.321, type III protein arginine methyltransferase and EC 2.1.1.322, type IV protein arginine methyltransferase
[EC 2.1.1.125 created 1999 (EC 2.1.1.23 created 1972, modified 1976, modified 1983, part incorporated 1999), deleted 2015]
 
 
EC 2.1.1.126      
Deleted entry: [myelin basic protein]-arginine N-methyltransferase. Now covered by EC 2.1.1.319, type I protein arginine methyltransferase, EC 2.1.1.320, type II protein arginine methyltransferase, EC 2.1.1.321, type III protein arginine methyltransferase and EC 2.1.1.322, type IV protein arginine methyltransferase
[EC 2.1.1.126 created 1999 (EC 2.1.1.23 created 1972, modified 1976, modified 1983, part incorporated 1999), deleted 2015]
 
 
EC 2.1.1.127     
Accepted name: [ribulose-bisphosphate carboxylase]-lysine N-methyltransferase
Reaction: 3 S-adenosyl-L-methionine + [ribulose-1,5-bisphosphate carboxylase]-L-lysine = 3 S-adenosyl-L-homocysteine + [ribulose-1,5-bisphosphate carboxylase]-N6,N6,N6-trimethyl-L-lysine
Other name(s): rubisco methyltransferase; ribulose-bisphosphate-carboxylase/oxygenase N-methyltransferase; ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit εN-methyltransferase; S-adenosyl-L-methionine:[3-phospho-D-glycerate-carboxy-lyase (dimerizing)]-lysine 6-N-methyltransferase; RuBisCO methyltransferase; RuBisCO LSMT
Systematic name: S-adenosyl-L-methionine:[3-phospho-D-glycerate-carboxy-lyase (dimerizing)]-lysine N6-methyltransferase
Comments: The enzyme catalyses three successive methylations of Lys-14 in the large subunits of hexadecameric higher plant ribulose-bisphosphate-carboxylase (EC 4.1.1.39). Only the three methylated form is observed [3]. The enzyme from pea (Pisum sativum) also three-methylates a specific lysine in the chloroplastic isoforms of fructose-bisphosphate aldolase (EC 4.1.2.13) [5].
References:
1.  Wang, P., Royer, M., Houtz, R.L. Affinity purification of ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit εN-methyltransferase. Protein Expr. Purif. 6 (1995) 528–536. [PMID: 8527940]
2.  Ying, Z., Janney, N., Houtz, R.L. Organization and characterization of the ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit N-methyltransferase gene in tobacco. Plant Mol. Biol. 32 (1996) 663–672. [PMID: 8980518]
3.  Dirk, L.M., Flynn, E.M., Dietzel, K., Couture, J.F., Trievel, R.C. and Houtz, R.L. Kinetic manifestation of processivity during multiple methylations catalyzed by SET domain protein methyltransferases. Biochemistry 46 (2007) 3905–3915. [PMID: 17338551]
4.  Magnani, R., Nayak, N.R., Mazarei, M., Dirk, L.M. and Houtz, R.L. Polypeptide substrate specificity of PsLSMT. A set domain protein methyltransferase. J. Biol. Chem. 282 (2007) 27857–27864. [PMID: 17635932]
5.  Mininno, M., Brugiere, S., Pautre, V., Gilgen, A., Ma, S., Ferro, M., Tardif, M., Alban, C. and Ravanel, S. Characterization of chloroplastic fructose 1,6-bisphosphate aldolases as lysine-methylated proteins in plants. J. Biol. Chem. 287 (2012) 21034–21044. [PMID: 22547063]
[EC 2.1.1.127 created 1999, modified 2012]
 
 
EC 2.1.1.128     
Accepted name: (RS)-norcoclaurine 6-O-methyltransferase
Reaction: S-adenosyl-L-methionine + (RS)-norcoclaurine = S-adenosyl-L-homocysteine + (RS)-coclaurine
Glossary: norcoclaurine = 6,7-dihydroxy-1-[(4-hydroxyphenyl)methyl]-1,2,3,4-tetrahydroisoquinoline
Systematic name: S-adenosyl-L-methionine:(RS)-norcoclaurine 6-O-methyltransferase
Comments: The enzyme will also catalyse the 6-O-methylation of (RS)-norlaudanosoline to form 6-O-methyl-norlaudanosoline, but this alkaloid has not been found to occur in plants.
References:
1.  Rueffer, M., Nagakura, N., Zenk, M.H. Partial purification and properties of S-adenosyl-L-methionine:(R),(S)-norlaudanosoline-6-O-methyltransferase from Argemone platyceras cell cultures. Planta Med. 49 (1983) 131–137. [PMID: 17405035]
2.  Sato, F., Tsujita, T., Katagiri, Y., Yoshida, S. and Yamada, Y. Purification and characterization of S-adenosyl-L-methionine:norcoclaurine 6-O-methyltransferase from cultured Coptis japonica cells. Eur. J. Biochem. 225 (1994) 125–131. [PMID: 7925429]
3.  Stadler, R., Zenk, M.H. A revision of the generally accepted pathway for the biosynthesis of the benzyltetrahydroisoquinoline reticuline. Liebigs Ann. Chem. (1990) 555–562.
[EC 2.1.1.128 created 1999]
 
 
EC 2.1.1.129     
Accepted name: inositol 4-methyltransferase
Reaction: S-adenosyl-L-methionine + myo-inositol = S-adenosyl-L-homocysteine + 1D-4-O-methyl-myo-inositol
Other name(s): myo-inositol 4-O-methyltransferase; S-adenosyl-L-methionine:myo-inositol 4-O-methyltransferase; myo-inositol 6-O-methyltransferase
Systematic name: S-adenosyl-L-methionine:1D-myo-inositol 4-methyltransferase
Comments: The enzyme from the rice bean Vigna umbellata (Fabaceae) is highly specific for S-adenosyl-L-methionine. The enzyme also methylates 1L-1,2,4/3,5-cyclohexanepentol, 2,4,6/3,5-pentahydroxycyclohexanone, D,L-2,3,4,6/5-pentacyclohexanone and 2,2′-anhydro-2-C-hydroxymethyl-myo-inositol, but at lower rates than that of myo-inositol.
References:
1.  Vernon, D.M., Bohnert, H.J. A novel methyl transferase induced by osmotic stress in the facultative halophyte Mesembryanthemum crystallinum. EMBO J. 11 (1992) 2077–2085. [PMID: 1600940]
2.  Wanek, W. and Richter, A. Purification and characterization of myo-inositol 6-O-methyltransferase from Vigna umbellata Ohwi et Ohashi. Planta 197 (1995) 427–434.
[EC 2.1.1.129 created 1999 (EC 2.1.1.134 created 1999, incorporated 2002), modified 2002]
 
 
EC 2.1.1.130     
Accepted name: precorrin-2 C20-methyltransferase
Reaction: S-adenosyl-L-methionine + precorrin-2 = S-adenosyl-L-homocysteine + precorrin-3A
Systematic name: S-adenosyl-L-methionine:precorrin-2 C20-methyltransferase
References:
1.  Roessner, C.A., Warren, M.J., Santander, P.J., Atshaves, B.P., Ozaki, S., Stolowich, N.J., Iida, K., Scott, A.I. Expression of Salmonella typhimurium enzymes for cobinamide synthesis. Identification of the 11-methyl and 20-methyl transferases of corrin biosynthesis. FEBS Lett. 301 (1992) 73–78. [PMID: 1451790]
2.  Roessner, C.A., Spencer, J.B., Ozaki, S., Min, C., Atshaves, B.P., Nayar, P., Anousis, N., Stolowich, N.J., Holderman, M.T., Scott, A.I. Overexpression in Escherichia coli of 12 vitamin B12 biosynthetic enzymes. Protein Extr. Purif. 6 (1995) 155–163. [PMID: 7606163]
3.  Debussche, L., Thibaut, D., Cameron, B., Crouzet, J. and Blanche, F. Biosynthesis of the corrin macrocycle of coenzyme B12 in Pseudomonas denitrificans. J. Bacteriol. 175 (1993) 7430–7440. [PMID: 8226690]
[EC 2.1.1.130 created 1999]
 
 
EC 2.1.1.131     
Accepted name: precorrin-3B C17-methyltransferase
Reaction: S-adenosyl-L-methionine + precorrin-3B = S-adenosyl-L-homocysteine + precorrin-4
Other name(s): precorrin-3 methyltransferase; CobJ
Systematic name: S-adenosyl-L-methionine:precorrin-3B C17-methyltransferase
Comments: In the aerobic cobalamin biosythesis pathway, four enzymes are involved in the conversion of precorrin-3A to precorrin-6A. The first of the four steps is carried out by EC 1.14.13.83, precorrin-3B synthase (CobG), yielding precorrin-3B as the product. This is followed by three methylation reactions, which introduce a methyl group at C-17 (CobJ; EC 2.1.1.131), C-11 (CobM; EC 2.1.1.133) and C-1 (CobF; EC 2.1.1.152) of the macrocycle, giving rise to precorrin-4, precorrin-5 and precorrin-6A, respectively.
References:
1.  Scott, A.I., Roessner, C.A., Stolowich, N.J., Spencer, J.B., Min, C. and Ozaki, S.I. Biosynthesis of vitamin B12. Discovery of the enzymes for oxidative ring contraction and insertion of the fourth methyl group. FEBS Lett. 331 (1993) 105–108. [PMID: 8405386]
2.  Debussche, L., Thibaut, D., Cameron, B., Crouzet, J. and Blanche, F. Biosynthesis of the corrin macrocycle of coenzyme B12 in Pseudomonas denitrificans. J. Bacteriol. 175 (1993) 7430–7440. [PMID: 8226690]
[EC 2.1.1.131 created 1999]
 
 
EC 2.1.1.132     
Accepted name: precorrin-6B C5,15-methyltransferase (decarboxylating)
Reaction: 2 S-adenosyl-L-methionine + precorrin-6B = 2 S-adenosyl-L-homocysteine + precorrin-8X + CO2 (overall reaction)
(1a) S-adenosyl-L-methionine + precorrin-6B = S-adenosyl-L-homocysteine + precorrin-7 + CO2
(1b) S-adenosyl-L-methionine + precorrin-7 = S-adenosyl-L-homocysteine + precorrin-8X
Glossary: precorrin-6B = precorrin-6Y
Other name(s): precorrin-6 methyltransferase; precorrin-6Y methylase; precorrin-6Y C5,15-methyltransferase (decarboxylating); cobL (gene name)
Systematic name: S-adenosyl-L-methionine:1-precorrin-6B C5,15-methyltransferase (C-12-decarboxylating)
Comments: The enzyme, which participates in the aerobic adenosylcobalamin biosynthesis pathway, has S-adenosyl-L-methionine-dependent methyltransferase and decarboxylase activities. The enzyme is a fusion protein with two active sites; one catalyses the methylation at C15 and the decarboxylation, while the other catalyses the methylation at C5.
References:
1.  Blanche, F., Famechon, A., Thibaut, D., Debussche, L., Cameron, B., Crouzet, J. Biosynthesis of vitamin B12 in Pseudomonas denitrificans: the biosynthetic sequence from precorrin-6Y to precorrin-8X is catalyzed by the cobL gene product. J. Bacteriol. 174 (1992) 1050–1052. [PMID: 1732195]
2.  Deery, E., Schroeder, S., Lawrence, A.D., Taylor, S.L., Seyedarabi, A., Waterman, J., Wilson, K.S., Brown, D., Geeves, M.A., Howard, M.J., Pickersgill, R.W. and Warren, M.J. An enzyme-trap approach allows isolation of intermediates in cobalamin biosynthesis. Nat. Chem. Biol. 8 (2012) 933–940. [PMID: 23042036]
[EC 2.1.1.132 created 1999, modified 2013]
 
 
EC 2.1.1.133     
Accepted name: precorrin-4 C11-methyltransferase
Reaction: S-adenosyl-L-methionine + precorrin-4 = S-adenosyl-L-homocysteine + precorrin-5
Other name(s): precorrin-3 methylase; CobM
Systematic name: S-adenosyl-L-methionine:precorrin-4 C11 methyltransferase
Comments: In the aerobic cobalamin biosythesis pathway, four enzymes are involved in the conversion of precorrin-3A to precorrin-6A. The first of the four steps is carried out by EC 1.14.13.83, precorrin-3B synthase (CobG), yielding precorrin-3B as the product. This is followed by three methylation reactions, which introduce a methyl group at C-17 (CobJ; EC 2.1.1.131), C-11 (CobM; EC 2.1.1.133) and C-1 (CobF; EC 2.1.1.152) of the macrocycle, giving rise to precorrin-4, precorrin-5 and precorrin-6A, respectively.
References:
1.  Crouzet, J., Cameron, B., Cauchois, L., Rigault, S., Rouyez, M.C., Blanche, F. , Thibaut D., Debussche, L. Genetic and sequence analysis of an 8.7-kilobase Pseudomonas denitrificans fragment carrying eight genes involved in transformation of precorrin-2 to cobyrinic acid. J. Bacteriol. 172 (1990) 5980–5990. [PMID: 2211521]
2.  Roth, J.R., Lawrence, J.G., Rubenfield, M., Kieffer-Higgins, S., Church, G.M. Characterization of the cobalamin (vitamin B12) biosynthetic genes of Salmonella typhimurium. J. Bacteriol. 175 (1993) 3303–3316. [PMID: 8501034]
[EC 2.1.1.133 created 1999]
 
 
EC 2.1.1.134      
Deleted entry:  myo-inositol 6-O-methyltransferase. Now included with EC 2.1.1.129, inositol 4-methyltransferase
[EC 2.1.1.134 created 1999, deleted 2002]
 
 
EC 2.1.1.135      
Transferred entry: [methionine synthase]-cobalamin methyltransferase (cob(II)alamin reducing). Now EC 1.16.1.8, [methionine synthase] reductase
[EC 2.1.1.135 created 1999, deleted 2003]
 
 
EC 2.1.1.136     
Accepted name: chlorophenol O-methyltransferase
Reaction: S-adenosyl-L-methionine + trichlorophenol = S-adenosyl-L-homocysteine + trichloroanisole
Other name(s): halogenated phenol O-methyltransferase, trichlorophenol O-methyltransferase
Systematic name: S-adenosyl-L-methionine:trichlorophenol O-methyltransferase
Comments: The enzyme from Trichoderma virgatum, when cultured in the presence of halogenated phenol, also acts on a range of mono-, di- and trichlorophenols.
References:
1.  Kikuchi, T. and Oe, T. Halogenated phenol O-methyltransferase, its production and deodorization using the same. Patent JP9234062, Chem. Abstr. (1994), 127, 27468.
[EC 2.1.1.136 created 2000]
 
 
EC 2.1.1.137     
Accepted name: arsenite methyltransferase
Reaction: (1) S-adenosyl-L-methionine + arsenite = S-adenosyl-L-homocysteine + methylarsonate
(2) S-adenosyl-L-methionine + methylarsonite = S-adenosyl-L-homocysteine + dimethylarsinate
Other name(s): S-adenosyl-L-methionine:arsenic(III) methyltransferase; S-adenosyl-L-methionine:methylarsonite As-methyltransferase; methylarsonite methyltransferase
Systematic name: S-adenosyl-L-methionine:arsenite As-methyltransferase
Comments: An enzyme of the biotransformation pathway that forms dimethylarsinate from inorganic arsenite and arsenate. It methylates arsenite to form methylarsonate, Me-AsO3H2, which is reduced by EC 1.20.4.2, methylarsonate reductase, to methylarsonite, Me-As(OH)2. Methylarsonite is also a substrate for this enzyme (EC 2.1.1.137), which converts it into the much less toxic compound dimethylarsinate (cacodylate), Me2As(O)-OH.
References:
1.  Zakharyan, R.A. and Aposhian, H.V. Enzymatic reduction of arsenic compounds in mammalian systems: the rate-limiting enzyme of rabbit liver arsenic biotransformation is MMA(V) reductase. Chem. Res. Toxicol. 12 (1999) 1278–1283. [PMID: 10604879]
2.  Zakharyan, R.A., Ayala-Fierro, F., Cullen, W.R., Carter, D.M. and Aposhian, H.V. Enzymatic methylation of arsenic compounds. VII. Monomethylarsonous acid (MMAIII) is the substrate for MMA methyltransferase of rabbit liver and human hepatocytes. Toxicol. Appl. Pharmacol. 158 (1999) 9–15. [PMID: 10387927]
3.  Zakharyan, R.A., Wildfang, E. and Aposhian, H.V. Enzymatic methylation of arsenic compounds. III. The marmoset and tamarin, but not the rhesus, monkeys are deficient in methyltransferases that methylate inorganic arsenic. Toxicol. Appl. Pharmacol. 140 (1996) 77–84. [PMID: 8806872]
4.  Zakharyan, R.A., Wu, Y., Bogdan, G.M. and Aposhian, H.V. Enzymatic methylation of arsenic compounds: assay, partial purification, and properties of arsenite methyltransferase and monomethylarsonic acid methyltransferase of rabbit liver. Chem. Res. Toxicol. 8 (1995) 1029–1038. [PMID: 8605285]
5.  Lin, S., Shi, Q., Nix, F.B., Styblo, M., Beck, M.A., Herbin-Davis, K.M., Hall, L.L., Simeonsson, J.B. and Thomas, D.J. A novel S-adenosyl-L-methionine:arsenic(III) methyltransferase from rat liver cytosol. J. Biol. Chem. 277 (2002) 10795–10803. [PMID: 11790780]
[EC 2.1.1.137 created 2000, (EC 2.1.1.138 incorporated 2003), modified 2003]
 
 
EC 2.1.1.138      
Deleted entry:  methylarsonite methyltransferase. Reaction due to EC 2.1.1.137, arsonite methyltransferase
[EC 2.1.1.138 created 2000, deleted 2003]
 
 
EC 2.1.1.139     
Accepted name: 3′-demethylstaurosporine O-methyltransferase
Reaction: S-adenosyl-L-methionine + 3′-demethylstaurosporine = S-adenosyl-L-homocysteine + staurosporine
Other name(s): 3′-demethoxy-3′-hydroxystaurosporine O-methyltransferase; staurosporine synthase
Systematic name: S-adenosyl-L-methionine:3′-demethylstaurosporine O-methyltransferase
Comments: Catalyses the final step in the biosynthesis of staurosporine, an alkaloidal antibiotic that is a potent inhibitor of protein kinases, especially protein kinase C.
References:
1.  Weidner, S., Kittelmann, M., Goeke, K., Ghisalba, O. and Zahner, H. 3′-Demethoxy-3′-hydroxystaurosporine-O-methyltransferase from Streptomyces longisporoflavus catalyzing the last step in the biosynthesis of staurosporine. J. Antibiot. (Tokyo) 51 (1998) 679–682. [PMID: 9727395]
[EC 2.1.1.139 created 2000]
 
 
EC 2.1.1.140     
Accepted name: (S)-coclaurine-N-methyltransferase
Reaction: S-adenosyl-L-methionine + (S)-coclaurine = S-adenosyl-L-homocysteine + (S)-N-methylcoclaurine
Systematic name: S-adenosyl-L-methionine:(S)-coclaurine-N-methyltransferase
Comments: The enzyme is specific for the (S)-isomer of coclaurine. Norcoclaurine can also act as an acceptor.
References:
1.  Loeffler, S., Deus-Neumann, B. and Zenk, M.H. S-Adenosyl-L-methionine: (S)-coclaurine-N-methyltransferase from Tinospora cordifolia. Phytochemistry 38 (1995) 1387–1395.
[EC 2.1.1.140 created 2001]
 
 
EC 2.1.1.141     
Accepted name: jasmonate O-methyltransferase
Reaction: S-adenosyl-L-methionine + jasmonate = S-adenosyl-L-homocysteine + methyl jasmonate
Glossary: jasmonic acid = {(1R,2R)-3-oxo-2-[(Z)pent-2-enyl]cyclopent-2-enyl}acetic acid
Other name(s): jasmonic acid carboxyl methyltransferase
Systematic name: S-adenosyl-L-methionine:jasmonate O-methyltransferase
Comments: 9,10-Dihydrojasmonic acid is a poor substrate for the enzyme. The enzyme does not convert 12-oxo-phytodienoic acid (a precursor of jasmonic acid), salicylic acid, benzoic acid, linolenic acid or cinnamic acid into their corresponding methyl esters. Enzyme activity is inhibited by the presence of divalent cations, e.g., Ca2+, Cu2+, Mg2+ and Zn2+.
References:
1.  Seo, H.S., Song, J.T., Cheong, J.J., Lee, Y.H., Lee, Y.W., Hwang, I., Lee, J.S. and Choi, Y.D. Jasmonic acid carboxyl methyltransferase: A key enzyme for jasmonate-regulated plant responses. Proc. Natl. Acad. Sci. USA 98 (2001) 4788–4793. [PMID: 11287667]
[EC 2.1.1.141 created 2001]
 
 
EC 2.1.1.142     
Accepted name: cycloartenol 24-C-methyltransferase
Reaction: S-adenosyl-L-methionine + cycloartenol = S-adenosyl-L-homocysteine + cyclolaudenol
Glossary: cyclolaudenol = (24S)-24-methylcycloart-25-en-3β-ol
Other name(s): sterol C-methyltransferase
Systematic name: S-adenosyl-L-methionine:cycloartenol 24-C-methyltransferase
Comments: S-Adenosyl-L-methionine methylates the Si face of the 24(25)-double bond with elimination of a hydrogen atom from the pro-Z methyl group at C-25.
References:
1.  Mangla, A.T. and Nes, W.D. Sterol C-methyl transferase from Prototheca wickerhamii mechanism, sterol specificity and inhibition. Bioorg. Med. Chem. 8 (2000) 925. [PMID: 10882005]
[EC 2.1.1.142 created 2001, modified 2019]
 
 
EC 2.1.1.143     
Accepted name: 24-methylenesterol C-methyltransferase
Reaction: S-adenosyl-L-methionine + 24-methylenelophenol = S-adenosyl-L-homocysteine + (Z)-24-ethylidenelophenol
Glossary: lophenol = 4α-methyl-5α-cholesta-7-en-3β-ol
Other name(s): SMT2; 24-methylenelophenol C-241-methyltransferase
Systematic name: S-adenosyl-L-methionine:24-methylenelophenol C-methyltransferase
Comments: This is the second methylation step of plant sterol biosynthesis (cf EC 2.1.1.142, cycloartenol 24-C-methyltransferase).
References:
1.  Bouvier-Navé, P., Husselstein, T. and Benveniste, P. Two families of sterol methyltransferases are involved in the first and the second methylation steps of plant biosynthesis. Eur. J. Biochem. 256 (1998) 88–96. [PMID: 9746350]
[EC 2.1.1.143 created 2001]
 
 
EC 2.1.1.144     
Accepted name: trans-aconitate 2-methyltransferase
Reaction: S-adenosyl-L-methionine + trans-aconitate = S-adenosyl-L-homocysteine + (E)-3-(methoxycarbonyl)pent-2-enedioate
Glossary: trans-aconitate = (E)-prop-1-ene-1,2,3-tricarboxylate
Systematic name: S-adenosyl-L-methionine:(E)-prop-1-ene-1,2,3-tricarboxylate 2′-O-methyltransferase
Comments: Also catalyses the formation of the methyl monoester of cis-aconitate, isocitrate and citrate, but more slowly. While the enzyme from Escherichia coli forms (E)-3-(methoxycarbonyl)-pent-2-enedioate as the product, that from Saccharomyces cerevisiae forms (E)-2-(methoxycarbonylmethyl)butenedioate and is therefore classified as a separate enzyme (cf. EC 2.1.1.145, trans-aconitate 3-methyltransferase).
References:
1.  Cai, H. and Clarke, S. A novel methyltransferase catalyzes the esterification of trans-aconitate in Escherichia coli. J. Biol. Chem. 274 (1999) 13470–13479. [PMID: 10224113]
2.  Cai, H., Strouse, J., Dumlao, D., Jung, M.E. and Clarke, S. Distinct reactions catalyzed by bacterial and yeast trans-aconitate methyltransferase. Biochemistry 40 (2001) 2210–2219. [PMID: 11329290]
3.  Cai, H., Dumlao, D., Katz, J.E. and Clarke, S. Identification of the gene and characterization of the activity of the trans-aconitate methyltransferase from Saccharomyces cerevisiae. Biochemistry 40 (2001) 13699–13709. [PMID: 11695919]
[EC 2.1.1.144 created 2002]
 
 
EC 2.1.1.145     
Accepted name: trans-aconitate 3-methyltransferase
Reaction: S-adenosyl-L-methionine + trans-aconitate = S-adenosyl-L-homocysteine + (E)-2-(methoxycarbonylmethyl)butenedioate
Glossary: trans-aconitate = (E)-prop-1-ene-1,2,3-tricarboxylate
Systematic name: S-adenosyl-L-methionine:(E)-prop-1-ene-1,2,3-tricarboxylate 3′-O-methyltransferase
Comments: Also catalyses the formation of the methyl monoester of cis-aconitate, isocitrate and citrate, but more slowly. While the enzyme from Saccharomyces cerevisiae forms (E)-2-(methoxycarbonylmethyl)butenedioate as the product, that from Escherichia coli forms (E)-3-(methoxycarbonyl)-pent-2-enedioate and is therefore classified as a separate enzyme (cf. EC 2.1.1.144, trans-aconitate 2-methyltransferase)
References:
1.  Cai, H. and Clarke, S. A novel methyltransferase catalyzes the esterification of trans-aconitate in Escherichia coli. J. Biol. Chem. 274 (1999) 13470–13479. [PMID: 10224113]
2.  Cai, H., Strouse, J., Dumlao, D., Jung, M.E. and Clarke, S. Distinct reactions catalyzed by bacterial and yeast trans-aconitate methyltransferase. Biochemistry 40 (2001) 2210–2219. [PMID: 11329290]
[EC 2.1.1.145 created 2002]
 
 
EC 2.1.1.146     
Accepted name: (iso)eugenol O-methyltransferase
Reaction: S-adenosyl-L-methionine + isoeugenol = S-adenosyl-L-homocysteine + isomethyleugenol
Systematic name: S-adenosyl-L-methionine:isoeugenol O-methyltransferase
Comments: Acts on eugenol and chavicol as well as isoeugenol.
References:
1.  Wang, J. and Pichersky, E. Characterization of S-adenosyl-L-methionine:(iso)eugenol O-methyltransferase involved in floral scent production in Clarkia breweri. Arch. Biochem. Biophys. 349 (1998) 153–160. [PMID: 9439593]
2.  Gang, D.R., Lavid, N., Zubieta, C., Chen, F., Beuerle, T., Lewinsohn, E., Noel, J.P. and Pichersky, E. Characterization of phenylpropene O-methyltransferases from sweet basil: facile change of substrate specificity and convergent evolution within a plant O-methyltransferase family. Plant Cell 14 (2002) 505–519. [PMID: 11884690]
[EC 2.1.1.146 created 2002]
 
 
EC 2.1.1.147     
Accepted name: corydaline synthase
Reaction: S-adenosyl-L-methionine + palmatine + 2 NADPH + H+ = S-adenosyl-L-homocysteine + corydaline + 2 NADP+
Systematic name: S-adenosyl-L-methionine:protoberberine 13-C-methyltransferase
Comments: Also acts on 7,8-dihydropalmatine.
References:
1.  Rueffer, M., Bauer, W. and Zenk, M.H. The formation of corydaline and related alkaloids in Corydalis cava in vivo and in vitro. Canad. J. Chem. 72 (1994) 170–175.
[EC 2.1.1.147 created 2002]
 
 
EC 2.1.1.148     
Accepted name: thymidylate synthase (FAD)
Reaction: 5,10-methylenetetrahydrofolate + dUMP + NADPH + H+ = dTMP + tetrahydrofolate + NADP+
Other name(s): Thy1; ThyX
Systematic name: 5,10-methylenetetrahydrofolate,FADH2:dUMP C-methyltransferase
Comments: Contains FAD. All thymidylate synthases catalyse a reductive methylation involving the transfer of the methylene group of 5,10-methylenetetrahydrofolate to the C5 position of dUMP and a two electron reduction of the methylene group to a methyl group. Unlike the classical thymidylate synthase, ThyA (EC 2.1.1.45), which uses folate as both a 1-carbon donor and a source of reducing equivalents, this enzyme uses a flavin coenzyme as a source of reducing equivalents, which are derived from NADPH.
References:
1.  Myllykallio, H., Lipowski, G., Leduc, D., Filee, J., Forterre, P. and Liebl, U. An alternative flavin-dependent mechanism for thymidylate synthesis. Science 297 (2002) 105–107. [PMID: 12029065]
2.  Griffin, J., Roshick, C., Iliffe-Lee, E. and McClarty, G. Catalytic mechanism of Chlamydia trachomatis flavin-dependent thymidylate synthase. J. Biol. Chem. 280 (2005) 5456–5467. [PMID: 15591067]
3.  Graziani, S., Bernauer, J., Skouloubris, S., Graille, M., Zhou, C.Z., Marchand, C., Decottignies, P., van Tilbeurgh, H., Myllykallio, H. and Liebl, U. Catalytic mechanism and structure of viral flavin-dependent thymidylate synthase ThyX. J. Biol. Chem. 281 (2006) 24048–24057. [PMID: 16707489]
4.  Koehn, E.M., Fleischmann, T., Conrad, J.A., Palfey, B.A., Lesley, S.A., Mathews, I.I. and Kohen, A. An unusual mechanism of thymidylate biosynthesis in organisms containing the thyX gene. Nature 458 (2009) 919–923. [PMID: 19370033]
5.  Koehn, E.M. and Kohen, A. Flavin-dependent thymidylate synthase: a novel pathway towards thymine. Arch. Biochem. Biophys. 493 (2010) 96–102. [PMID: 19643076]
6.  Mishanina, T.V., Yu, L., Karunaratne, K., Mondal, D., Corcoran, J.M., Choi, M.A. and Kohen, A. An unprecedented mechanism of nucleotide methylation in organisms containing thyX. Science 351 (2016) 507–510. [PMID: 26823429]
[EC 2.1.1.148 created 2003, modified 2010]
 
 
EC 2.1.1.149      
Deleted entry: myricetin O-methyltransferase. Now covered by EC 2.1.1.267, flavonoid 3′,5′-methyltransferase.
[EC 2.1.1.149 created 2003, modified 2011, deleted 2013]
 
 
EC 2.1.1.150     
Accepted name: isoflavone 7-O-methyltransferase
Reaction: S-adenosyl-L-methionine + a 7-hydroxyisoflavone = S-adenosyl-L-homocysteine + a 7-methoxyisoflavone
Systematic name: S-adenosyl-L-methionine:hydroxyisoflavone 7-O-methyltransferase
Comments: The enzyme from alfalfa can methylate daidzein, genistein and 6,7,4′-trihydroxyisoflavone but not flavones or flavanones.
References:
1.  Edwards, R. and Dixon, R.A. Isoflavone O-methyltransferase activities in elicitor-treated cell suspension cultures of Medicago sativa. Phytochemistry 30 (1991) 2597–2606.
2.  He, X.Z. and Dixon, R.A. Genetic manipulation of isoflavone 7-O-methyltransferase enhances biosynthesis of 4′-O-methylated isoflavonoid phytoalexins and disease resistance in alfalfa. Plant Cell 12 (2000) 1689–1702. [PMID: 11006341]
3.  He, X.-Z. and Dixon, R.A. Affinity chromatography, substrate/product specificity, and amino acid sequence analysis of an isoflavone O-methyltransferase from alfalfa (Medicago sativa L.). Arch. Biochem. Biophys. 336 (1996) 121–129. [PMID: 8951042]
4.  He, X.Z., Reddy, J.T. and Dixon, R.A. Stress responses in alfalfa (Medicago sativa L). XXII. cDNA cloning and characterization of an elicitor-inducible isoflavone 7-O-methyltransferase. Plant Mol. Biol. 36 (1998) 43–54. [PMID: 9484461]
5.  Liu, C.-J. and Dixon, R.A. Elicitor-induced association of isoflavone O-methyltransferase with endomembranes prevents the formation and 7-O-methylation of daidzein during isoflavonoid phytoalexin biosynthesis. Plant Cell 13 (2001) 2643–2658. [PMID: 11752378]
6.  Zubieta, C., He, X.-Z., Dixon, R.A. and Noel, J.P. Structures of two natural product methyltransferases reveal the basis for substrate specificity in plant O-methyltransferases. Nat. Struct. Biol. 8 (2001) 271–279. [PMID: 11224575]
[EC 2.1.1.150 created 2003]
 
 
EC 2.1.1.151     
Accepted name: cobalt-factor II C20-methyltransferase
Reaction: S-adenosyl-L-methionine + cobalt-factor II = S-adenosyl-L-homocysteine + cobalt-factor III
Other name(s): CbiL
Systematic name: S-adenosyl-L-methionine:cobalt-factor-II C20-methyltransferase
Comments: Involved in the anaerobic biosynthesis of vitamin B12.
References:
1.  Spencer, P., Stolowich, N.J., Sumner, L.W. and Scott, A.I. Definition of the redox states of cobalt-precorrinoids: investigation of the substrate and redox specificity of CbiL from Salmonella typhimurium. Biochemistry 37 (1998) 14917–14927. [PMID: 9778368]
[EC 2.1.1.151 created 2004]
 
 
EC 2.1.1.152     
Accepted name: precorrin-6A synthase (deacetylating)
Reaction: S-adenosyl-L-methionine + precorrin-5 + H2O = S-adenosyl-L-homocysteine + precorrin-6A + acetate
Other name(s): precorrin-6X synthase (deacetylating); CobF
Systematic name: S-adenosyl-L-methionine:precorrin-5 C1-methyltransferase (deacetylating)
Comments: In the aerobic cobalamin biosythesis pathway, four enzymes are involved in the conversion of precorrin-3A to precorrin-6A. The first of the four steps is carried out by EC 1.14.13.83, precorrin-3B synthase (CobG), yielding precorrin-3B as the product. This is followed by three methylation reactions, which introduce a methyl group at C-17 (CobJ; EC 2.1.1.131), C-11 (CobM; EC 2.1.1.133) and C-1 (CobF; EC 2.1.1.152) of the macrocycle, giving rise to precorrin-4, precorrin-5 and precorrin-6A, respectively.
References:
1.  Debussche, L., Thibaut, D., Cameron, B., Crouzet, J. and Blanche, F. Biosynthesis of the corrin macrocycle of coenzyme B12 in Pseudomonas denitrificans. J. Bacteriol. 175 (1993) 7430–7440. [PMID: 8226690]
2.  Warren, M.J., Raux, E., Schubert, H.L. and Escalante-Semerena, J.C. The biosynthesis of adenosylcobalamin (vitamin B12). Nat. Prod. Rep. 19 (2002) 390–412. [PMID: 12195810]
[EC 2.1.1.152 created 2004]
 
 
EC 2.1.1.153     
Accepted name: vitexin 2′′-O-rhamnoside 7-O-methyltransferase
Reaction: S-adenosyl-L-methionine + vitexin 2′′-O-β-L-rhamnoside = S-adenosyl-L-homocysteine + 7-O-methylvitexin 2′′-O-β-L-rhamnoside
Systematic name: S-adenosyl-L-methionine:vitexin-2′′-O-β-L-rhamnoside 7-O-methyltransferase
Comments: The flavonoids vitexin and isovitexin 2′′-O-arabinoside do not act as substrates for the enzyme from oats (Avena sativa).
References:
1.  Knogge, W. and Weissenbock, G. Purification, characterization, and kinetic mechanism of S-adenosyl-L-methionine: vitexin 2′′-O-rhamnoside 7-O-methyltransferase of Avena sativa L. Eur. J. Biochem. 140 (1984) 113–118. [PMID: 6705789]
[EC 2.1.1.153 created 2004]
 
 
EC 2.1.1.154     
Accepted name: isoliquiritigenin 2′-O-methyltransferase
Reaction: S-adenosyl-L-methionine + isoliquiritigenin = S-adenosyl-L-homocysteine + 2′-O-methylisoliquiritigenin
Glossary: isoliquiritigenin = 4,2′,4′-trihydroxychalcone
Other name(s): chalcone OMT; CHMT
Systematic name: S-adenosyl-L-methionine:isoliquiritigenin 2′-O-methyltransferase
Comments: Not identical to EC 2.1.1.65, licodione 2′-O-methyltransferase [2]. While EC 2.1.1.154, isoliquiritigenin 2′-O-methyltransferase can use licodione as a substrate, EC 2.1.1.65 cannot use isoliquiritigenin as a substrate.
References:
1.  Maxwell, C.A., Edwards, R. and Dixon, R.A. Identification, purification, and characterization of S-adenosyl-L-methionine: isoliquiritigenin 2′-O-methyltransferase from alfalfa (Medicago sativa L.). Arch. Biochem. Biophys. 293 (1992) 158–166. [PMID: 1731632]
2.  Ichimura, M., Furuno, T., Takahashi, T., Dixon, R.A. and Ayabe, S. Enzymic O-methylation of isoliquiritigenin and licodione in alfalfa and licorice cultures. Phytochemistry 44 (1997) 991–995. [PMID: 9055445]
[EC 2.1.1.154 created 2004]
 
 
EC 2.1.1.155     
Accepted name: kaempferol 4′-O-methyltransferase
Reaction: S-adenosyl-L-methionine + kaempferol = S-adenosyl-L-homocysteine + kaempferide
Glossary: kaempferide = 3,5,7-trihydroxy-4′-methoxyflavone
Other name(s): S-adenosyl-L-methionine:flavonoid 4′-O-methyltransferase; F 4′-OMT
Systematic name: S-adenosyl-L-methionine:kaempferol 4′-O-methyltransferase
Comments: The enzyme acts on the hydroxy group in the 4′-position of some flavones, flavanones and isoflavones. Kaempferol, apigenin and kaempferol triglucoside are substrates, as is genistein, which reacts more slowly. Compounds with an hydroxy group in the 3′ and 4′ positions, such as quercetin and eriodictyol, do not act as substrates. Similar to EC 2.1.1.75, apigenin 4′-O-methyltransferase and EC 2.1.1.83, 3,7-dimethylquercetin 4′-O-methyltransferase.
References:
1.  Curir, P., Lanzotti, V., Dolci, M., Dolci, P., Pasini, C. and Tollin, G. Purification and properties of a new S-adenosyl-L-methionine:flavonoid 4′-O-methyltransferase from carnation (Dianthus caryophyllus L.). Eur. J. Biochem. 270 (2003) 3422–3431. [PMID: 12899699]
[EC 2.1.1.155 created 2004]
 
 
EC 2.1.1.156     
Accepted name: glycine/sarcosine N-methyltransferase
Reaction: 2 S-adenosyl-L-methionine + glycine = 2 S-adenosyl-L-homocysteine + N,N-dimethylglycine (overall reaction)
(1a) S-adenosyl-L-methionine + glycine = S-adenosyl-L-homocysteine + sarcosine
(1b) S-adenosyl-L-methionine + sarcosine = S-adenosyl-L-homocysteine + N,N-dimethylglycine
Glossary: sarcosine = N-methylglycine
Other name(s): ApGSMT; glycine-sarcosine methyltransferase; GSMT; GMT; glycine sarcosine N-methyltransferase; S-adenosyl-L-methionine:sarcosine N-methyltransferase
Systematic name: S-adenosyl-L-methionine:glycine(or sarcosine) N-methyltransferase [sarcosine(or N,N-dimethylglycine)-forming]
Comments: Cells of the oxygen-evolving halotolerant cyanobacterium Aphanocthece halophytica synthesize betaine from glycine by a three-step methylation process. This is the first enzyme and it leads to the formation of either sarcosine or N,N-dimethylglycine, which is further methylated to yield betaine (N,N,N-trimethylglycine) by the action of EC 2.1.1.157, sarcosine/dimethylglycine N-methyltransferase. Differs from EC 2.1.1.20, glycine N-methyltransferase, as it can further methylate the product of the first reaction. Acetate, dimethylglycine and S-adenosyl-L-homocysteine can inhibit the reaction [3].
References:
1.  Nyyssölä, A., Kerovuo, J., Kaukinen, P., von Weymarn, N. and Reinikainen, T. Extreme halophiles synthesize betaine from glycine by methylation. J. Biol. Chem. 275 (2000) 22196–22201. [PMID: 10896953]
2.  Nyyssölä, A., Reinikainen, T. and Leisola, M. Characterization of glycine sarcosine N-methyltransferase and sarcosine dimethylglycine N-methyltransferase. Appl. Environ. Microbiol. 67 (2001) 2044–2050. [PMID: 11319079]
3.  Waditee, R., Tanaka, Y., Aoki, K., Hibino, T., Jikuya, H., Takano, J., Takabe, T. and Takabe, T. Isolation and functional characterization of N-methyltransferases that catalyze betaine synthesis from glycine in a halotolerant photosynthetic organism Aphanothece halophytica. J. Biol. Chem. 278 (2003) 4932–4942. [PMID: 12466265]
[EC 2.1.1.156 created 2005]
 
 
EC 2.1.1.157     
Accepted name: sarcosine/dimethylglycine N-methyltransferase
Reaction: 2 S-adenosyl-L-methionine + sarcosine = 2 S-adenosyl-L-homocysteine + betaine (overall reaction)
(1a) S-adenosyl-L-methionine + sarcosine = S-adenosyl-L-homocysteine + N,N-dimethylglycine
(1b) S-adenosyl-L-methionine + N,N-dimethylglycine = S-adenosyl-L-homocysteine + betaine
Glossary: sarcosine = N-methylglycine
betaine = glycine betaine = N,N,N-trimethylglycine = N,N,N-trimethylammonioacetate
Other name(s): ApDMT; sarcosine-dimethylglycine methyltransferase; SDMT; sarcosine dimethylglycine N-methyltransferase; S-adenosyl-L-methionine:N,N-dimethylglycine N-methyltransferase
Systematic name: S-adenosyl-L-methionine:sarcosine(or N,N-dimethylglycine) N-methyltransferase [N,N-dimethylglycine(or betaine)-forming]
Comments: Cells of the oxygen-evolving halotolerant cyanobacterium Aphanocthece halophytica synthesize betaine from glycine by a three-step methylation process. The first enzyme, EC 2.1.1.156, glycine/sarcosine N-methyltransferase, leads to the formation of either sarcosine or N,N-dimethylglycine, which is further methylated to yield betaine (N,N,N-trimethylglycine) by the action of this enzyme. Both of these enzymes can catalyse the formation of N,N-dimethylglycine from sarcosine [3]. The reactions are strongly inhibited by S-adenosyl-L-homocysteine.
References:
1.  Nyyssölä, A., Kerovuo, J., Kaukinen, P., von Weymarn, N. and Reinikainen, T. Extreme halophiles synthesize betaine from glycine by methylation. J. Biol. Chem. 275 (2000) 22196–22201. [PMID: 10896953]
2.  Nyyssölä, A., Reinikainen, T. and Leisola, M. Characterization of glycine sarcosine N-methyltransferase and sarcosine dimethylglycine N-methyltransferase. Appl. Environ. Microbiol. 67 (2001) 2044–2050. [PMID: 11319079]
3.  Waditee, R., Tanaka, Y., Aoki, K., Hibino, T., Jikuya, H., Takano, J., Takabe, T. and Takabe, T. Isolation and functional characterization of N-methyltransferases that catalyze betaine synthesis from glycine in a halotolerant photosynthetic organism Aphanothece halophytica. J. Biol. Chem. 278 (2003) 4932–4942. [PMID: 12466265]
[EC 2.1.1.157 created 2005, modified 2010]
 
 
EC 2.1.1.158     
Accepted name: 7-methylxanthosine synthase
Reaction: S-adenosyl-L-methionine + xanthosine = S-adenosyl-L-homocysteine + 7-methylxanthosine
Other name(s): xanthosine methyltransferase; XMT; xanthosine:S-adenosyl-L-methionine methyltransferase; CtCS1; CmXRS1; CaXMT1; S-adenosyl-L-methionine:xanthosine 7-N-methyltransferase
Systematic name: S-adenosyl-L-methionine:xanthosine N7-methyltransferase
Comments: The enzyme is specific for xanthosine, as XMP and xanthine cannot act as substrates [2,4]. The enzyme does not have N1- or N3- methylation activity [2]. This is the first methylation step in the production of caffeine.
References:
1.  Negishi, O., Ozawa, T. and Imagawa, H. The role of xanthosine in the biosynthesis of caffeine in coffee plants. Agric. Biol. Chem. 49 (1985) 2221–2222.
2.  Mizuno, K., Kato, M., Irino, F., Yoneyama, N., Fujimura, T. and Ashihara, H. The first committed step reaction of caffeine biosynthesis: 7-methylxanthosine synthase is closely homologous to caffeine synthases in coffee (Coffea arabica L.). FEBS Lett. 547 (2003) 56–60. [PMID: 12860386]
3.  Uefuji, H., Ogita, S., Yamaguchi, Y., Koizumi, N. and Sano, H. Molecular cloning and functional characterization of three distinct N-methyltransferases involved in the caffeine biosynthetic pathway in coffee plants. Plant Physiol. 132 (2003) 372–380. [PMID: 12746542]
4.  Yoneyama, N., Morimoto, H., Ye, C.X., Ashihara, H., Mizuno, K. and Kato, M. Substrate specificity of N-methyltransferase involved in purine alkaloids synthesis is dependent upon one amino acid residue of the enzyme. Mol. Genet. Genomics 275 (2006) 125–135. [PMID: 16333668]
[EC 2.1.1.158 created 2007]
 
 
EC 2.1.1.159     
Accepted name: theobromine synthase
Reaction: S-adenosyl-L-methionine + 7-methylxanthine = S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
Glossary: theobromine = 3,7-dimethylxanthine
paraxanthine = 1,7-dimethylxanthine
Other name(s): monomethylxanthine methyltransferase; MXMT; CTS1; CTS2; S-adenosyl-L-methionine:7-methylxanthine 3-N-methyltransferase
Systematic name: S-adenosyl-L-methionine:7-methylxanthine N3-methyltransferase
Comments: This is the third enzyme in the caffeine-biosynthesis pathway. This enzyme can also catalyse the conversion of paraxanthine into caffeine, although the paraxanthine pathway is considered to be a minor pathway for caffeine biosynthesis [2,3].
References:
1.  Ogawa, M., Herai, Y., Koizumi, N., Kusano, T. and Sano, H. 7-Methylxanthine methyltransferase of coffee plants. Gene isolation and enzymatic properties. J. Biol. Chem. 276 (2001) 8213–8218. [PMID: 11108716]
2.  Uefuji, H., Ogita, S., Yamaguchi, Y., Koizumi, N. and Sano, H. Molecular cloning and functional characterization of three distinct N-methyltransferases involved in the caffeine biosynthetic pathway in coffee plants. Plant Physiol. 132 (2003) 372–380. [PMID: 12746542]
3.  Yoneyama, N., Morimoto, H., Ye, C.X., Ashihara, H., Mizuno, K. and Kato, M. Substrate specificity of N-methyltransferase involved in purine alkaloids synthesis is dependent upon one amino acid residue of the enzyme. Mol. Genet. Genomics 275 (2006) 125–135. [PMID: 16333668]
[EC 2.1.1.159 created 2007]
 
 
EC 2.1.1.160     
Accepted name: caffeine synthase
Reaction: (1) S-adenosyl-L-methionine + 3,7-dimethylxanthine = S-adenosyl-L-homocysteine + 1,3,7-trimethylxanthine
(2) S-adenosyl-L-methionine + 1,7-dimethylxanthine = S-adenosyl-L-homocysteine + 1,3,7-trimethylxanthine
(3) S-adenosyl-L-methionine + 7-methylxanthine = S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
Glossary: theobromine = 3,7-dimethylxanthine
paraxanthine = 1,7-dimethylxanthine
caffeine = 1,3,7-trimethylxanthine
Other name(s): dimethylxanthine methyltransferase; 3N-methyltransferase; DXMT; CCS1; S-adenosyl-L-methionine:3,7-dimethylxanthine 1-N-methyltransferase
Systematic name: S-adenosyl-L-methionine:3,7-dimethylxanthine N1-methyltransferase
Comments: Paraxanthine is the best substrate for this enzyme but the paraxanthine pathway is considered to be a minor pathway for caffeine biosynthesis [2,3].
References:
1.  Kato, M., Mizuno, K., Fujimura, T., Iwama, M., Irie, M., Crozier, A. and Ashihara, H. Purification and characterization of caffeine synthase from tea leaves. Plant Physiol. 120 (1999) 579–586. [PMID: 10364410]
2.  Mizuno, K., Okuda, A., Kato, M., Yoneyama, N., Tanaka, H., Ashihara, H. and Fujimura, T. Isolation of a new dual-functional caffeine synthase gene encoding an enzyme for the conversion of 7-methylxanthine to caffeine from coffee (Coffea arabica L.). FEBS Lett. 534 (2003) 75–81. [PMID: 12527364]
3.  Uefuji, H., Ogita, S., Yamaguchi, Y., Koizumi, N. and Sano, H. Molecular cloning and functional characterization of three distinct N-methyltransferases involved in the caffeine biosynthetic pathway in coffee plants. Plant Physiol. 132 (2003) 372–380. [PMID: 12746542]
4.  Kato, M., Mizuno, K., Crozier, A., Fujimura, T. and Ashihara, H. Caffeine synthase gene from tea leaves. Nature 406 (2000) 956–957. [PMID: 10984041]
[EC 2.1.1.160 created 2007]
 
 
EC 2.1.1.161     
Accepted name: dimethylglycine N-methyltransferase
Reaction: S-adenosyl-L-methionine + N,N-dimethylglycine = S-adenosyl-L-homocysteine + betaine
Glossary: betaine = glycine betaine = N,N,N-trimethylglycine = N,N,N-trimethylammonioacetate
Other name(s): BsmB; DMT
Systematic name: S-adenosyl-L-methionine:N,N-dimethylglycine N-methyltransferase (betaine-forming)
Comments: This enzyme, from the marine cyanobacterium Synechococcus sp. WH8102, differs from EC 2.1.1.157, sarcosine/dimethylglycine N-methyltransferase in that it cannot use sarcosine as an alternative substrate [1]. Betaine is a ’compatible solute’ that enables cyanobacteria to cope with osmotic stress by maintaining a positive cellular turgor.
References:
1.  Lu, W.D., Chi, Z.M. and Su, C.D. Identification of glycine betaine as compatible solute in Synechococcus sp. WH8102 and characterization of its N-methyltransferase genes involved in betaine synthesis. Arch. Microbiol. 186 (2006) 495–506. [PMID: 17019606]
[EC 2.1.1.161 created 2007]
 
 
EC 2.1.1.162     
Accepted name: glycine/sarcosine/dimethylglycine N-methyltransferase
Reaction: 3 S-adenosyl-L-methionine + glycine = 3 S-adenosyl-L-homocysteine + betaine (overall reaction)
(1a) S-adenosyl-L-methionine + glycine = S-adenosyl-L-homocysteine + sarcosine
(1b) S-adenosyl-L-methionine + sarcosine = S-adenosyl-L-homocysteine + N,N-dimethylglycine
(1c) S-adenosyl-L-methionine + N,N-dimethylglycine = S-adenosyl-L-homocysteine + betaine
Glossary: sarcosine = N-methylglycine
betaine = glycine betaine = N,N,N-trimethylglycine = N,N,N-trimethylammonioacetate
Other name(s): GSDMT; glycine sarcosine dimethylglycine N-methyltransferase
Systematic name: S-adenosyl-L-methionine:glycine(or sarcosine or N,N-dimethylglycine) N-methyltransferase [sarcosine(or N,N-dimethylglycine or betaine)-forming]
Comments: Unlike EC 2.1.1.156 (glycine/sarcosine N-methyltransferase), EC 2.1.1.157 (sarcosine/dimethylglycine N-methyltransferase) and EC 2.1.1.161 (dimethylglycine N-methyltransferase), this enzyme, from the halophilic methanoarchaeon Methanohalophilus portucalensis, can methylate glycine and all of its intermediates to form the compatible solute betaine [1].
References:
1.  Lai, M.C., Wang, C.C., Chuang, M.J., Wu, Y.C. and Lee, Y.C. Effects of substrate and potassium on the betaine-synthesizing enzyme glycine sarcosine dimethylglycine N-methyltransferase from a halophilic methanoarchaeon Methanohalophilus portucalensis. Res. Microbiol. 157 (2006) 948–955. [PMID: 17098399]
[EC 2.1.1.162 created 2007]
 
 
EC 2.1.1.163     
Accepted name: demethylmenaquinone methyltransferase
Reaction: a demethylmenaquinol + S-adenosyl-L-methionine = a menaquinol + S-adenosyl-L-homocysteine
Other name(s): S-adenosyl-L-methione—DMK methyltransferase; demethylmenaquinone C-methylase; 2-heptaprenyl-1,4-naphthoquinone methyltransferase; 2-demethylmenaquinone methyltransferase; S-adenosyl-L-methione:2-demethylmenaquinone methyltransferase
Systematic name: S-adenosyl-L-methione:demethylmenaquinone methyltransferase
Comments: The enzyme catalyses the last step in menaquinone biosynthesis. It is able to accept substrates with varying polyprenyl side chain length (the chain length is determined by polyprenyl diphosphate synthase)[1]. The enzyme from Escherichia coli also catalyses the conversion of 2-methoxy-6-octaprenyl-1,4-benzoquinone to 5-methoxy-2-methyl-3-octaprenyl-1,4-benzoquinone during the biosynthesis of ubiquinone [4]. The enzyme probably acts on menaquinol rather than menaquinone.
References:
1.  Koike-Takeshita, A., Koyama, T. and Ogura, K. Identification of a novel gene cluster participating in menaquinone (vitamin K2) biosynthesis. Cloning and sequence determination of the 2-heptaprenyl-1,4-naphthoquinone methyltransferase gene of Bacillus stearothermophilus. J. Biol. Chem. 272 (1997) 12380–12383. [PMID: 9139683]
2.  Wissenbach, U., Ternes, D. and Unden, G. An Escherichia coli mutant containing only demethylmenaquinone, but no menaquinone: effects on fumarate, dimethylsulfoxide, trimethylamine N-oxide and nitrate respiration. Arch. Microbiol. 158 (1992) 68–73. [PMID: 1444716]
3.  Catala, F., Azerad, R. and Lederer, E. Sur les propriétés de la desméthylménaquinone C-méthylase de Mycobacterium phlei. Int. Z. Vitaminforsch. 40 (1970) 363–373. [PMID: 5450997]
4.  Lee, P.T., Hsu, A.Y., Ha, H.T. and Clarke, C.F. A C-methyltransferase involved in both ubiquinone and menaquinone biosynthesis: isolation and identification of the Escherichia coli ubiE gene. J. Bacteriol. 179 (1997) 1748–1754. [PMID: 9045837]
[EC 2.1.1.163 created 2009]
 
 
EC 2.1.1.164     
Accepted name: demethylrebeccamycin-D-glucose O-methyltransferase
Reaction: 4′-demethylrebeccamycin + S-adenosyl-L-methionine = rebeccamycin + S-adenosyl-L-homocysteine
Other name(s): RebM
Systematic name: S-adenosyl-L-methionine:demethylrebeccamycin-D-glucose O-methyltransferase
Comments: Catalyses the last step in the biosynthesis of rebeccamycin, an indolocarbazole alkaloid produced by the bacterium Lechevalieria aerocolonigenes. The enzyme is able to use a wide variety substrates, tolerating variation on the imide heterocycle, deoxygenation of the sugar moiety, and even indolocarbazole glycoside anomers [1]. The enzyme is a member of the general acid/base-dependent O-methyltransferase family [2].
References:
1.  Zhang, C., Albermann, C., Fu, X., Peters, N.R., Chisholm, J.D., Zhang, G., Gilbert, E.J., Wang, P.G., Van Vranken, D.L. and Thorson, J.S. RebG- and RebM-catalyzed indolocarbazole diversification. ChemBioChem 7 (2006) 795–804. [PMID: 16575939]
2.  Singh, S., McCoy, J.G., Zhang, C., Bingman, C.A., Phillips, G.N., Jr. and Thorson, J.S. Structure and mechanism of the rebeccamycin sugar 4′-O-methyltransferase RebM. J. Biol. Chem. 283 (2008) 22628–22636. [PMID: 18502766]
[EC 2.1.1.164 created 2010]
 
 
EC 2.1.1.165     
Accepted name: methyl halide transferase
Reaction: S-adenosyl-L-methionine + iodide = S-adenosyl-L-homocysteine + methyl iodide
Other name(s): MCT; methyl chloride transferase; S-adenosyl-L-methionine:halide/bisulfide methyltransferase; AtHOL1; AtHOL2; AtHOL3; HARMLESS TO OZONE LAYER protein; HMT; S-adenosyl-L-methionine: halide ion methyltransferase; SAM:halide ion methyltransferase
Systematic name: S-adenosylmethionine:iodide methyltransferase
Comments: This enzyme contributes to the methyl halide emissions from Arabidopsis [6].
References:
1.  Ni, X. and Hager, L.P. Expression of Batis maritima methyl chloride transferase in Escherichia coli. Proc. Natl. Acad. Sci. USA 96 (1999) 3611–3615. [PMID: 10097085]
2.  Saxena, D., Aouad, S., Attieh, J. and Saini, H.S. Biochemical characterization of chloromethane emission from the wood-rotting fungus Phellinus pomaceus. Appl. Environ. Microbiol. 64 (1998) 2831–2835. [PMID: 9687437]
3.  Attieh, J.M., Hanson, A.D. and Saini, H.S. Purification and characterization of a novel methyltransferase responsible for biosynthesis of halomethanes and methanethiol in Brassica oleracea. J. Biol. Chem. 270 (1995) 9250–9257. [PMID: 7721844]
4.  Itoh, N., Toda, H., Matsuda, M., Negishi, T., Taniguchi, T. and Ohsawa, N. Involvement of S-adenosylmethionine-dependent halide/thiol methyltransferase (HTMT) in methyl halide emissions from agricultural plants: isolation and characterization of an HTMT-coding gene from Raphanus sativus (daikon radish). BMC Plant Biol. 9 (2009) 116. [PMID: 19723322]
5.  Ohsawa, N., Tsujita, M., Morikawa, S. and Itoh, N. Purification and characterization of a monohalomethane-producing enzyme S-adenosyl-L-methionine: halide ion methyltransferase from a marine microalga, Pavlova pinguis. Biosci. Biotechnol. Biochem. 65 (2001) 2397–2404. [PMID: 11791711]
6.  Nagatoshi, Y.and Nakamura, T. Characterization of three halide methyltransferases in Arabidopsis thaliana. Plant Biotechnol. 24 (2007) 503–506.
[EC 2.1.1.165 created 2010]
 
 
EC 2.1.1.166     
Accepted name: 23S rRNA (uridine2552-2′-O)-methyltransferase
Reaction: S-adenosyl-L-methionine + uridine2552 in 23S rRNA = S-adenosyl-L-homocysteine + 2′-O-methyluridine2552 in 23S rRNA
Other name(s): Um(2552) 23S ribosomal RNA methyltransferase; heat shock protein RrmJ; RrmJ; FTSJ; Um2552 methyltransferase
Systematic name: S-adenosyl-L-methionine:23S rRNA (uridine2552-2′-O-)-methyltransferase
Comments: The enzyme catalyses the 2′-O-methylation of the universally conserved U2552 in the A loop of 23S rRNA [3].
References:
1.  Caldas, T., Binet, E., Bouloc, P., Costa, A., Desgres, J. and Richarme, G. The FtsJ/RrmJ heat shock protein of Escherichia coli is a 23 S ribosomal RNA methyltransferase. J. Biol. Chem. 275 (2000) 16414–16419. [PMID: 10748051]
2.  Hager, J., Staker, B.L., Bugl, H. and Jakob, U. Active site in RrmJ, a heat shock-induced methyltransferase. J. Biol. Chem. 277 (2002) 41978–41986. [PMID: 12181314]
3.  Hager, J., Staker, B.L. and Jakob, U. Substrate binding analysis of the 23S rRNA methyltransferase RrmJ. J. Bacteriol. 186 (2004) 6634–6642. [PMID: 15375145]
4.  Bugl, H., Fauman, E.B., Staker, B.L., Zheng, F., Kushner, S.R., Saper, M.A., Bardwell, J.C. and Jakob, U. RNA methylation under heat shock control. Mol. Cell 6 (2000) 349–360. [PMID: 10983982]
[EC 2.1.1.166 created 2010]
 
 
EC 2.1.1.167     
Accepted name: 27S pre-rRNA (guanosine2922-2′-O)-methyltransferase
Reaction: S-adenosyl-L-methionine + guanosine2922 in 27S pre-rRNA = S-adenosyl-L-homocysteine + 2′-O-methylguanosine2922 in 27S pre-rRNA
Other name(s): Spb1p (gene name); YCL054W (gene name)
Systematic name: S-adenosyl-L-methionine:27S pre-rRNA (guanosine2922-2′-O-)-methyltransferase
Comments: Spb1p is a site-specific 2′-O-ribose RNA methyltransferase that catalyses the formation of 2′-O-methylguanosine2922, a universally conserved position of the catalytic center of the ribosome that is essential for translation. 2′-O-Methylguanosine2922 is formed at a later stage of the processing, during the maturation of of the 27S pre-rRNA. In absence of snR52, Spb1p can also catalyse the formation of uridine2921 [1].
References:
1.  Lapeyre, B. and Purushothaman, S.K. Spb1p-directed formation of Gm2922 in the ribosome catalytic center occurs at a late processing stage. Mol. Cell 16 (2004) 663–669. [PMID: 15546625]
2.  Bonnerot, C., Pintard, L. and Lutfalla, G. Functional redundancy of Spb1p and a snR52-dependent mechanism for the 2′-O-ribose methylation of a conserved rRNA position in yeast. Mol. Cell 12 (2003) 1309–1315. [PMID: 14636587]
[EC 2.1.1.167 created 2010]
 
 
EC 2.1.1.168     
Accepted name: 21S rRNA (uridine2791-2′-O)-methyltransferase
Reaction: S-adenosyl-L-methionine + uridine2791 in 21S rRNA = S-adenosyl-L-homocysteine + 2′-O-methyluridine2791 in 21S rRNA
Other name(s): MRM2 (gene name); mitochondrial 21S rRNA methyltransferase; mitochondrial rRNA MTase 2
Systematic name: S-adenosyl-L-methionine:21S rRNA (uridine2791-2′-O-)-methyltransferase
Comments: The enzyme catalyses the methylation of uridine2791 of mitochondrial 21S rRNA.
References:
1.  Pintard, L., Bujnicki, J.M., Lapeyre, B. and Bonnerot, C. MRM2 encodes a novel yeast mitochondrial 21S rRNA methyltransferase. EMBO J. 21 (2002) 1139–1147. [PMID: 11867542]
[EC 2.1.1.168 created 2010]
 
 
EC 2.1.1.169     
Accepted name: tricetin 3′,4′,5′-O-trimethyltransferase
Reaction: 3 S-adenosyl-L-methionine + tricetin = 3 S-adenosyl-L-homocysteine + 3′,4′,5′-O-trimethyltricetin (overall reaction)
(1a) S-adenosyl-L-methionine + tricetin = S-adenosyl-L-homocysteine + 3′-O-methyltricetin
(1b) S-adenosyl-L-methionine + 3′-O-methyltricetin = S-adenosyl-L-homocysteine + 3′,5′-O-dimethyltricetin
(1c) S-adenosyl-L-methionine + 3′,5′-O-dimethyltricetin = S-adenosyl-L-homocysteine + 3′,4′,5′-O-trimethyltricetin
Other name(s): FOMT; TaOMT1; TaCOMT1; TaOMT2
Systematic name: S-adenosyl-L-methionine:tricetin 3′,4′,5′-O-trimethyltransferase
Comments: The enzyme from Triticum aestivum catalyses the sequential O-methylation of tricetin via 3′-O-methyltricetin, 3′,5′-O-methyltricetin to 3′,4′,5′-O-trimethyltricetin [2].
References:
1.  Kornblatt, J.A., Zhou, J.M. and Ibrahim, R.K. Structure-activity relationships of wheat flavone O-methyltransferase: a homodimer of convenience. FEBS J. 275 (2008) 2255–2266. [PMID: 18397325]
2.  Zhou, J.M., Gold, N.D., Martin, V.J., Wollenweber, E. and Ibrahim, R.K. Sequential O-methylation of tricetin by a single gene product in wheat. Biochim. Biophys. Acta 1760 (2006) 1115–1124. [PMID: 16730127]
3.  Zhou, J.M., Seo, Y.W. and Ibrahim, R.K. Biochemical characterization of a putative wheat caffeic acid O-methyltransferase. Plant Physiol. Biochem. 47 (2009) 322–326. [PMID: 19211254]
[EC 2.1.1.169 created 2010]
 
 
EC 2.1.1.170     
Accepted name: 16S rRNA (guanine527-N7)-methyltransferase
Reaction: S-adenosyl-L-methionine + guanine527 in 16S rRNA = S-adenosyl-L-homocysteine + N7-methylguanine527 in 16S rRNA
Other name(s): ribosomal RNA small subunit methyltransferase G; 16S rRNA methyltransferase RsmG; GidB; rsmG (gene name)
Systematic name: S-adenosyl-L-methionine:16S rRNA (guanine527-N7)-methyltransferase
Comments: The enzyme specifically methylates guanine527 at N7 in 16S rRNA.
References:
1.  Okamoto, S., Tamaru, A., Nakajima, C., Nishimura, K., Tanaka, Y., Tokuyama, S., Suzuki, Y. and Ochi, K. Loss of a conserved 7-methylguanosine modification in 16S rRNA confers low-level streptomycin resistance in bacteria. Mol. Microbiol. 63 (2007) 1096–1106. [PMID: 17238915]
2.  Romanowski, M.J., Bonanno, J.B. and Burley, S.K. Crystal structure of the Escherichia coli glucose-inhibited division protein B (GidB) reveals a methyltransferase fold. Proteins 47 (2002) 563–567. [PMID: 12001236]
[EC 2.1.1.170 created 2010]
 
 
EC 2.1.1.171     
Accepted name: 16S rRNA (guanine966-N2)-methyltransferase
Reaction: S-adenosyl-L-methionine + guanine966 in 16S rRNA = S-adenosyl-L-homocysteine + N2-methylguanine966 in 16S rRNA
Other name(s): yhhF (gene name); rsmD (gene name); m2G966 methyltransferase
Systematic name: S-adenosyl-L-methionine:16S rRNA (guanine966-N2)-methyltransferase
Comments: The enzyme efficiently methylates guanine966 of the assembled 30S subunits in vitro. Protein-free 16S rRNA is not a substrate for RsmD [1]. The enzyme specifically methylates guanine966 at N2 in 16S rRNA.
References:
1.  Lesnyak, D.V., Osipiuk, J., Skarina, T., Sergiev, P.V., Bogdanov, A.A., Edwards, A., Savchenko, A., Joachimiak, A. and Dontsova, O.A. Methyltransferase that modifies guanine 966 of the 16 S rRNA: functional identification and tertiary structure. J. Biol. Chem. 282 (2007) 5880–5887. [PMID: 17189261]
[EC 2.1.1.171 created 1976 as EC 2.1.1.52, part transferred 2010 to EC 2.1.1.171]
 
 
EC 2.1.1.172     
Accepted name: 16S rRNA (guanine1207-N2)-methyltransferase
Reaction: S-adenosyl-L-methionine + guanine1207 in 16S rRNA = S-adenosyl-L-homocysteine + N2-methylguanine1207 in 16S rRNA
Other name(s): m2G1207 methyltransferase
Systematic name: S-adenosyl-L-methionine:16S rRNA (guanine1207-N2)-methyltransferase
Comments: The enzyme reacts well with 30S subunits reconstituted from 16S RNA transcripts and 30S proteins but is almost inactive with the corresponding free RNA [1]. The enzyme specifically methylates guanine1207 at N2 in 16S rRNA.
References:
1.  Tscherne, J.S., Nurse, K., Popienick, P. and Ofengand, J. Purification, cloning, and characterization of the 16 S RNA m2G1207 methyltransferase from Escherichia coli. J. Biol. Chem. 274 (1999) 924–929. [PMID: 9873033]
2.  Sunita, S., Purta, E., Durawa, M., Tkaczuk, K.L., Swaathi, J., Bujnicki, J.M. and Sivaraman, J. Functional specialization of domains tandemly duplicated within 16S rRNA methyltransferase RsmC. Nucleic Acids Res. 35 (2007) 4264–4274. [PMID: 17576679]
[EC 2.1.1.172 created 1976 as EC 2.1.1.52, part transferred 2010 to EC 2.1.1.172]
 
 
EC 2.1.1.173     
Accepted name: 23S rRNA (guanine2445-N2)-methyltransferase
Reaction: S-adenosyl-L-methionine + guanine2445 in 23S rRNA = S-adenosyl-L-homocysteine + N2-methylguanine2445 in 23S rRNA
Other name(s): ycbY (gene name); rlmL (gene name)
Systematic name: S-adenosyl-L-methionine:23S rRNA (guanine2445-N2)-methyltransferase
Comments: The enzyme methylates 23S rRNA in vitro, assembled 50S subunits are not a substrate [1]. The enzyme specifically methylates guanine2445 at N2 in 23S rRNA.
References:
1.  Lesnyak, D.V., Sergiev, P.V., Bogdanov, A.A. and Dontsova, O.A. Identification of Escherichia coli m2G methyltransferases: I. the ycbY gene encodes a methyltransferase specific for G2445 of the 23 S rRNA. J. Mol. Biol. 364 (2006) 20–25. [PMID: 17010378]
[EC 2.1.1.173 created 1976 as EC 2.1.1.52, part transferred 2010 to EC 2.1.1.173]
 
 
EC 2.1.1.174     
Accepted name: 23S rRNA (guanine1835-N2)-methyltransferase
Reaction: S-adenosyl-L-methionine + guanine1835 in 23S rRNA = S-adenosyl-L-homocysteine + N2-methylguanine1835 in 23S rRNA
Other name(s): ygjO (gene name); rlmG (gene name); ribosomal RNA large subunit methyltransferase G
Systematic name: S-adenosyl-L-methionine:23S rRNA (guanine1835-N2)-methyltransferase
Comments: The enzyme methylates 23S rRNA in vitro, assembled 50S subunits are not a substrate [1]. The enzyme specifically methylates guanine1835 at N2 in 23S rRNA.
References:
1.  Sergiev, P.V., Lesnyak, D.V., Bogdanov, A.A. and Dontsova, O.A. Identification of Escherichia coli m2G methyltransferases: II. The ygjO gene encodes a methyltransferase specific for G1835 of the 23 S rRNA. J. Mol. Biol. 364 (2006) 26–31. [PMID: 17010380]
[EC 2.1.1.174 created 1976 as EC 2.1.1.52, part transferred 2010 to EC 2.1.1.174]
 
 
EC 2.1.1.175     
Accepted name: tricin synthase
Reaction: 2 S-adenosyl-L-methionine + tricetin = 2 S-adenosyl-L-homocysteine + 3′,5′-O-dimethyltricetin (overall reaction)
(1a) S-adenosyl-L-methionine + tricetin = S-adenosyl-L-homocysteine + 3′-O-methyltricetin
(1b) S-adenosyl-L-methionine + 3′-O-methyltricetin = S-adenosyl-L-homocysteine + 3′,5′-O-dimethyltricetin
Glossary: tricin = 3′,5′-O-dimethyltricetin
Other name(s): ROMT-17; ROMT-15; HvOMT1; ZmOMT1
Systematic name: S-adenosyl-L-methionine:tricetin 3′,5′-O-dimethyltransferase
Comments: The enzymes from Oryza sativa (ROMT-15 and ROMT-17) catalyses the stepwise methylation of tricetin to its 3′-mono- and 3′,5′-dimethyl ethers. In contrast with the wheat enzyme (EC 2.1.1.169, tricetin 3′,4′,5′-O-trimethyltransferase), tricetin dimethyl ether is not converted to its 3′,4′,5′-trimethylated ether derivative [1]. The enzymes from Hordeum vulgare (HvOMT1) and from Zea mays (ZmOMT1) form the 3′,5′-dimethyl derivative as the major product [2].
References:
1.  Lee, Y.J., Kim, B.G., Chong, Y., Lim, Y. and Ahn, J.H. Cation dependent O-methyltransferases from rice. Planta 227 (2008) 641–647. [PMID: 17943312]
2.  Zhou, J.-M., Fukushi, Y., Wollenweber, E., Ibrahim, R.K. Characterization of two O-methyltransferase-like genes in barley and maize. Pharm. Biol. 46 (2008) 26–34.
[EC 2.1.1.175 created 2010]
 
 
EC 2.1.1.176     
Accepted name: 16S rRNA (cytosine967-C5)-methyltransferase
Reaction: S-adenosyl-L-methionine + cytosine967 in 16S rRNA = S-adenosyl-L-homocysteine + 5-methylcytosine967 in 16S rRNA
Other name(s): rsmB (gene name); fmu (gene name); 16S rRNA m5C967 methyltransferase
Systematic name: S-adenosyl-L-methionine:16S rRNA (cytosine967-C5)-methyltransferase
Comments: The enzyme specifically methylates cytosine967 at C5 in 16S rRNA.
References:
1.  Tscherne, J.S., Nurse, K., Popienick, P., Michel, H., Sochacki, M. and Ofengand, J. Purification, cloning, and characterization of the 16S RNA m5C967 methyltransferase from Escherichia coli. Biochemistry 38 (1999) 1884–1892. [PMID: 10026269]
2.  Gu, X.R., Gustafsson, C., Ku, J., Yu, M. and Santi, D.V. Identification of the 16S rRNA m5C967 methyltransferase from Escherichia coli. Biochemistry 38 (1999) 4053–4057. [PMID: 10194318]
3.  Foster, P.G., Nunes, C.R., Greene, P., Moustakas, D. and Stroud, R.M. The first structure of an RNA m5C methyltransferase, Fmu, provides insight into catalytic mechanism and specific binding of RNA substrate. Structure 11 (2003) 1609–1620. [PMID: 14656444]
[EC 2.1.1.176 created 2010]
 
 
EC 2.1.1.177     
Accepted name: 23S rRNA (pseudouridine1915-N3)-methyltransferase
Reaction: S-adenosyl-L-methionine + pseudouridine1915 in 23S rRNA = S-adenosyl-L-homocysteine + N3-methylpseudouridine1915 in 23S rRNA
Other name(s): YbeA; RlmH; pseudouridine methyltransferase; m3Ψ methyltransferase; Ψ1915-specific methyltransferase; rRNA large subunit methyltransferase H
Systematic name: S-adenosyl-L-methionine:23S rRNA (pseudouridine1915-N3)-methyltransferase
Comments: YbeA does not methylate uridine at position 1915 [1].
References:
1.  Ero, R., Peil, L., Liiv, A. and Remme, J. Identification of pseudouridine methyltransferase in Escherichia coli. RNA 14 (2008) 2223–2233. [PMID: 18755836]
2.  Purta, E., Kaminska, K.H., Kasprzak, J.M., Bujnicki, J.M. and Douthwaite, S. YbeA is the m3Ψ methyltransferase RlmH that targets nucleotide 1915 in 23S rRNA. RNA 14 (2008) 2234–2244. [PMID: 18755835]
[EC 2.1.1.177 created 2010]
 
 
EC 2.1.1.178     
Accepted name: 16S rRNA (cytosine1407-C5)-methyltransferase
Reaction: S-adenosyl-L-methionine + cytosine1407 in 16S rRNA = S-adenosyl-L-homocysteine + 5-methylcytosine1407 in 16S rRNA
Other name(s): RNA m5C methyltransferase YebU; RsmF; YebU
Systematic name: S-adenosyl-L-methionine:16S rRNA (cytosine1407-C5)-methyltransferase
Comments: The enzyme specifically methylates cytosine1407 at C5 in 16S rRNA.
References:
1.  Andersen, N.M. and Douthwaite, S. YebU is a m5C methyltransferase specific for 16 S rRNA nucleotide 1407. J. Mol. Biol. 359 (2006) 777–786. [PMID: 16678201]
2.  Hallberg, B.M., Ericsson, U.B., Johnson, K.A., Andersen, N.M., Douthwaite, S., Nordlund, P., Beuscher, A.E., 4th and Erlandsen, H. The structure of the RNA m5C methyltransferase YebU from Escherichia coli reveals a C-terminal RNA-recruiting PUA domain. J. Mol. Biol. 360 (2006) 774–787. [PMID: 16793063]
[EC 2.1.1.178 created 2010]
 
 
EC 2.1.1.179     
Accepted name: 16S rRNA (guanine1405-N7)-methyltransferase
Reaction: S-adenosyl-L-methionine + guanine1405 in 16S rRNA = S-adenosyl-L-homocysteine + N7-methylguanine1405 in 16S rRNA
Other name(s): methyltransferase Sgm; m7G1405 Mtase; Sgm Mtase; Sgm; sisomicin-gentamicin methyltransferase; sisomicin-gentamicin methylase; GrmA; RmtB; RmtC; ArmA
Systematic name: S-adenosyl-L-methionine:16S rRNA (guanine1405-N7)-methyltransferase
Comments: The enzyme from the antibiotic-producing bacterium Micromonospora zionensis specifically methylates guanine1405 at N7 in 16S rRNA, thereby rendering the ribosome resistant to 4,6-disubstituted deoxystreptamine aminoglycosides, which include gentamicins and kanamycins [2].
References:
1.  Husain, N., Tkaczuk, K.L., Tulsidas, S.R., Kaminska, K.H., Cubrilo, S., Maravic-Vlahovicek, G., Bujnicki, J.M. and Sivaraman, J. Structural basis for the methylation of G1405 in 16S rRNA by aminoglycoside resistance methyltransferase Sgm from an antibiotic producer: a diversity of active sites in m7G methyltransferases. Nucleic Acids Res. 38 (2010) 4120–4132. [PMID: 20194115]
2.  Savic, M., Lovric, J., Tomic, T.I., Vasiljevic, B. and Conn, G.L. Determination of the target nucleosides for members of two families of 16S rRNA methyltransferases that confer resistance to partially overlapping groups of aminoglycoside antibiotics. Nucleic Acids Res. 37 (2009) 5420–5431. [PMID: 19589804]
3.  Tomic, T.I., Moric, I., Conn, G.L. and Vasiljevic, B. Aminoglycoside resistance genes sgm and kgmB protect bacterial but not yeast small ribosomal subunits in vitro despite high conservation of the rRNA A-site. Res. Microbiol. 159 (2008) 658–662. [PMID: 18930134]
4.  Savic, M., Ilic-Tomic, T., Macmaster, R., Vasiljevic, B. and Conn, G.L. Critical residues for cofactor binding and catalytic activity in the aminoglycoside resistance methyltransferase Sgm. J. Bacteriol. 190 (2008) 5855–5861. [PMID: 18586937]
5.  Maravic Vlahovicek, G., Cubrilo, S., Tkaczuk, K.L. and Bujnicki, J.M. Modeling and experimental analyses reveal a two-domain structure and amino acids important for the activity of aminoglycoside resistance methyltransferase Sgm. Biochim. Biophys. Acta 1784 (2008) 582–590. [PMID: 18343347]
6.  Kojic, M., Topisirovic, L. and Vasiljevic, B. Cloning and characterization of an aminoglycoside resistance determinant from Micromonospora zionensis. J. Bacteriol. 174 (1992) 7868–7872. [PMID: 1447159]
7.  Schmitt, E., Galimand, M., Panvert, M., Courvalin, P. and Mechulam, Y. Structural bases for 16 S rRNA methylation catalyzed by ArmA and RmtB methyltransferases. J. Mol. Biol. 388 (2009) 570–582. [PMID: 19303884]
8.  Wachino, J., Shibayama, K., Kimura, K., Yamane, K., Suzuki, S. and Arakawa, Y. RmtC introduces G1405 methylation in 16S rRNA and confers high-level aminoglycoside resistance on Gram-positive microorganisms. FEMS Microbiol. Lett. 311 (2010) 56–60. [PMID: 20722735]
9.  Liou, G.F., Yoshizawa, S., Courvalin, P. and Galimand, M. Aminoglycoside resistance by ArmA-mediated ribosomal 16S methylation in human bacterial pathogens. J. Mol. Biol. 359 (2006) 358–364. [PMID: 16626740]
[EC 2.1.1.179 created 2010]
 
 
EC 2.1.1.180     
Accepted name: 16S rRNA (adenine1408-N1)-methyltransferase
Reaction: S-adenosyl-L-methionine + adenine1408 in 16S rRNA = S-adenosyl-L-homocysteine + N1-methyladenine1408 in 16S rRNA
Other name(s): kanamycin-apramycin resistance methylase; 16S rRNA:m1A1408 methyltransferase; KamB; NpmA; 16S rRNA m1A1408 methyltransferase
Systematic name: S-adenosyl-L-methionine:16S rRNA (adenine1408-N1)-methyltransferase
Comments: The enzyme provides a panaminoglycoside-resistant nature through interference with the binding of aminoglycosides toward the A site of 16S rRNA through N1-methylation at position adenine1408 [4].
References:
1.  Beauclerk, A.A. and Cundliffe, E. Sites of action of two ribosomal RNA methylases responsible for resistance to aminoglycosides. J. Mol. Biol. 193 (1987) 661–671. [PMID: 2441068]
2.  Koscinski, L., Feder, M. and Bujnicki, J.M. Identification of a missing sequence and functionally important residues of 16S rRNA:m1A1408 methyltransferase KamB that causes bacterial resistance to aminoglycoside antibiotics. Cell Cycle 6 (2007) 1268–1271. [PMID: 17495534]
3.  Holmes, D.J., Drocourt, D., Tiraby, G. and Cundliffe, E. Cloning of an aminoglycoside-resistance-encoding gene, kamC, from Saccharopolyspora hirsuta: comparison with kamB from Streptomyces tenebrarius. Gene 102 (1991) 19–26. [PMID: 1840536]
4.  Wachino, J., Shibayama, K., Kurokawa, H., Kimura, K., Yamane, K., Suzuki, S., Shibata, N., Ike, Y. and Arakawa, Y. Novel plasmid-mediated 16S rRNA m1A1408 methyltransferase, NpmA, found in a clinically isolated Escherichia coli strain resistant to structurally diverse aminoglycosides. Antimicrob. Agents Chemother. 51 (2007) 4401–4409. [PMID: 17875999]
[EC 2.1.1.180 created 2010]
 
 
EC 2.1.1.181     
Accepted name: 23S rRNA (adenine1618-N6)-methyltransferase
Reaction: S-adenosyl-L-methionine + adenine1618 in 23S rRNA = S-adenosyl-L-homocysteine + N6-methyladenine1618 in 23S rRNA
Other name(s): rRNA large subunit methyltransferase F; YbiN protein; rlmF (gene name); m6A1618 methyltransferase
Systematic name: S-adenosyl-L-methionine:23S rRNA (adenine1618-N6)-methyltransferase
Comments: The recombinant YbiN protein is able to methylate partially deproteinized 50 S ribosomal subunit, but neither the completely assembled 50 S subunits nor completely deproteinized 23 S rRNA [1].
References:
1.  Sergiev, P.V., Serebryakova, M.V., Bogdanov, A.A. and Dontsova, O.A. The ybiN gene of Escherichia coli encodes adenine-N6 methyltransferase specific for modification of A1618 of 23 S ribosomal RNA, a methylated residue located close to the ribosomal exit tunnel. J. Mol. Biol. 375 (2008) 291–300. [PMID: 18021804]
[EC 2.1.1.181 created 1976 as EC 2.1.1.48, part transferred 2010 to EC 2.1.1.181]
 
 
EC 2.1.1.182     
Accepted name: 16S rRNA (adenine1518-N6/adenine1519-N6)-dimethyltransferase
Reaction: 4 S-adenosyl-L-methionine + adenine1518/adenine1519 in 16S rRNA = 4 S-adenosyl-L-homocysteine + N6-dimethyladenine1518/N6-dimethyladenine1519 in 16S rRNA
Other name(s): S-adenosylmethionine-6-N′,N′-adenosyl (rRNA) dimethyltransferase; KsgA; ksgA methyltransferase
Systematic name: S-adenosyl-L-methionine:16S rRNA (adenine1518-N6/adenine1519-N6)-dimethyltransferase
Comments: KsgA introduces the most highly conserved ribosomal RNA modification, the dimethylation of adenine1518 and adenine1519 in 16S rRNA. Strains lacking the methylase are resistant to kasugamycin [1].
References:
1.  Helser, T.L., Davies, J.E. and Dahlberg, J.E. Change in methylation of 16S ribosomal RNA associated with mutation to kasugamycin resistance in Escherichia coli. Nat. New Biol. 233 (1971) 12–14. [PMID: 4329247]
2.  Helser, T.L., Davies, J.E. and Dahlberg, J.E. Mechanism of kasugamycin resistance in Escherichia coli. Nat. New Biol. 235 (1972) 6–9. [PMID: 4336392]
3.  van Buul, C.P. and van Knippenberg, P.H. Nucleotide sequence of the ksgA gene of Escherichia coli: comparison of methyltransferases effecting dimethylation of adenosine in ribosomal RNA. Gene 38 (1985) 65–72. [PMID: 3905517]
4.  Formenoy, L.J., Cunningham, P.R., Nurse, K., Pleij, C.W. and Ofengand, J. Methylation of the conserved A1518-A1519 in Escherichia coli 16S ribosomal RNA by the ksgA methyltransferase is influenced by methylations around the similarly conserved U1512.G1523 base pair in the 3′ terminal hairpin. Biochimie 76 (1994) 1123–1128. [PMID: 7538324]
5.  O'Farrell, H.C., Scarsdale, J.N. and Rife, J.P. Crystal structure of KsgA, a universally conserved rRNA adenine dimethyltransferase in Escherichia coli. J. Mol. Biol. 339 (2004) 337–353. [PMID: 15136037]
6.  Poldermans, B., Roza, L. and Van Knippenberg, P.H. Studies on the function of two adjacent N6,N6-dimethyladenosines near the 3′ end of 16 S ribosomal RNA of Escherichia coli. III. Purification and properties of the methylating enzyme and methylase-30 S interactions. J. Biol. Chem. 254 (1979) 9094–9100. [PMID: 383712]
7.  Demirci, H., Belardinelli, R., Seri, E., Gregory, S.T., Gualerzi, C., Dahlberg, A.E. and Jogl, G. Structural rearrangements in the active site of the Thermus thermophilus 16S rRNA methyltransferase KsgA in a binary complex with 5′-methylthioadenosine. J. Mol. Biol. 388 (2009) 271–282. [PMID: 19285505]
8.  Tu, C., Tropea, J.E., Austin, B.P., Court, D.L., Waugh, D.S. and Ji, X. Structural basis for binding of RNA and cofactor by a KsgA methyltransferase. Structure 17 (2009) 374–385. [PMID: 19278652]
[EC 2.1.1.182 created 1976 as EC 2.1.1.48, part transferred 2010 to EC 2.1.1.182]
 
 
EC 2.1.1.183     
Accepted name: 18S rRNA (adenine1779-N6/adenine1780-N6)-dimethyltransferase
Reaction: 4 S-adenosyl-L-methionine + adenine1779/adenine1780 in 18S rRNA = 4 S-adenosyl-L-homocysteine + N6-dimethyladenine1779/N6-dimethyladenine1780 in 18S rRNA
Other name(s): 18S rRNA dimethylase Dim1p; Dim1p; ScDim1; m2(6)A dimethylase; KIDIM1
Systematic name: S-adenosyl-L-methionine:18S rRNA (adenine1779-N6/adenine1780-N6)-dimethyltransferase
Comments: DIM1 is involved in pre-rRNA processing [1].
References:
1.  Lafontaine, D., Vandenhaute, J. and Tollervey, D. The 18S rRNA dimethylase Dim1p is required for pre-ribosomal RNA processing in yeast. Genes Dev. 9 (1995) 2470–2481. [PMID: 7590228]
2.  Lafontaine, D.L., Preiss, T. and Tollervey, D. Yeast 18S rRNA dimethylase Dim1p: a quality control mechanism in ribosome synthesis. Mol. Cell Biol. 18 (1998) 2360–2370. [PMID: 9528805]
3.  Pulicherla, N., Pogorzala, L.A., Xu, Z., O'Farrell, H.C., Musayev, F.N., Scarsdale, J.N., Sia, E.A., Culver, G.M. and Rife, J.P. Structural and functional divergence within the Dim1/KsgA family of rRNA methyltransferases. J. Mol. Biol. 391 (2009) 884–893. [PMID: 19520088]
4.  Lafontaine, D., Delcour, J., Glasser, A.L., Desgres, J. and Vandenhaute, J. The DIM1 gene responsible for the conserved m6(2)Am6(2)A dimethylation in the 3′-terminal loop of 18 S rRNA is essential in yeast. J. Mol. Biol. 241 (1994) 492–497. [PMID: 8064863]
5.  O'Farrell, H.C., Pulicherla, N., Desai, P.M. and Rife, J.P. Recognition of a complex substrate by the KsgA/Dim1 family of enzymes has been conserved throughout evolution. RNA 12 (2006) 725–733. [PMID: 16540698]
[EC 2.1.1.183 created 1976 as EC 2.1.1.48, part transferred 2010 to EC 2.1.1.183]
 
 
EC 2.1.1.184     
Accepted name: 23S rRNA (adenine2085-N6)-dimethyltransferase
Reaction: 2 S-adenosyl-L-methionine + adenine2085 in 23S rRNA = 2 S-adenosyl-L-homocysteine + N6-dimethyladenine2085 in 23S rRNA
Other name(s): ErmC′ methyltransferase; ermC methylase; ermC 23S rRNA methyltransferase; rRNA:m6A methyltransferase ErmC′; ErmC′; rRNA methyltransferase ErmC′
Systematic name: S-adenosyl-L-methionine:23S rRNA (adenine2085-N6)-dimethyltransferase
Comments: ErmC is a methyltransferase that confers resistance to the macrolide-lincosamide-streptogramin B group of antibiotics by catalysing the methylation of 23S rRNA at adenine2085.
References:
1.  Zhong, P., Pratt, S.D., Edalji, R.P., Walter, K.A., Holzman, T.F., Shivakumar, A.G. and Katz, L. Substrate requirements for ErmC′ methyltransferase activity. J. Bacteriol. 177 (1995) 4327–4332. [PMID: 7543473]
2.  Denoya, C. and Dubnau, D. Mono- and dimethylating activities and kinetic studies of the ermC 23 S rRNA methyltransferase. J. Biol. Chem. 264 (1989) 2615–2624. [PMID: 2492520]
3.  Denoya, C.D. and Dubnau, D. Site and substrate specificity of the ermC 23S rRNA methyltransferase. J. Bacteriol. 169 (1987) 3857–3860. [PMID: 2440853]
4.  Bussiere, D.E., Muchmore, S.W., Dealwis, C.G., Schluckebier, G., Nienaber, V.L., Edalji, R.P., Walter, K.A., Ladror, U.S., Holzman, T.F. and Abad-Zapatero, C. Crystal structure of ErmC′, an rRNA methyltransferase which mediates antibiotic resistance in bacteria. Biochemistry 37 (1998) 7103–7112. [PMID: 9585521]
5.  Schluckebier, G., Zhong, P., Stewart, K.D., Kavanaugh, T.J. and Abad-Zapatero, C. The 2.2 Å structure of the rRNA methyltransferase ErmC′ and its complexes with cofactor and cofactor analogs: implications for the reaction mechanism. J. Mol. Biol. 289 (1999) 277–291. [PMID: 10366505]
6.  Maravic, G., Bujnicki, J.M., Feder, M., Pongor, S. and Flogel, M. Alanine-scanning mutagenesis of the predicted rRNA-binding domain of ErmC′ redefines the substrate-binding site and suggests a model for protein-RNA interactions. Nucleic Acids Res. 31 (2003) 4941–4949. [PMID: 12907737]
[EC 2.1.1.184 created 1976 as EC 2.1.1.48, part transferred 2010 to EC 2.1.1.184]
 
 
EC 2.1.1.185     
Accepted name: 23S rRNA (guanosine2251-2′-O)-methyltransferase
Reaction: S-adenosyl-L-methionine + guanosine2251 in 23S rRNA = S-adenosyl-L-homocysteine + 2′-O-methylguanosine2251 in 23S rRNA
Other name(s): rlmB (gene name); yifH (gene name)
Systematic name: S-adenosyl-L-methionine:23S rRNA (guanosine2251-2′-O-)-methyltransferase
Comments: The enzyme catalyses the methylation of guanosine2251, a modification conserved in the peptidyltransferase domain of 23S rRNA.
References:
1.  Lovgren, J.M. and Wikstrom, P.M. The rlmB gene is essential for formation of Gm2251 in 23S rRNA but not for ribosome maturation in Escherichia coli. J. Bacteriol. 183 (2001) 6957–6960. [PMID: 11698387]
2.  Michel, G., Sauve, V., Larocque, R., Li, Y., Matte, A. and Cygler, M. The structure of the RlmB 23S rRNA methyltransferase reveals a new methyltransferase fold with a unique knot. Structure 10 (2002) 1303–1315. [PMID: 12377117]
[EC 2.1.1.185 created 2010]
 
 
EC 2.1.1.186     
Accepted name: 23S rRNA (cytidine2498-2′-O)-methyltransferase
Reaction: S-adenosyl-L-methionine + cytidine2498 in 23S rRNA = S-adenosyl-L-homocysteine + 2′-O-methylcytidine2498 in 23S rRNA
Other name(s): YgdE; rRNA large subunit methyltransferase M; RlmM
Systematic name: S-adenosyl-L-methionine:23S rRNA (cytidine2498-2′-O-)-methyltransferase
References:
1.  Purta, E., O'Connor, M., Bujnicki, J.M. and Douthwaite, S. YgdE is the 2′-O-ribose methyltransferase RlmM specific for nucleotide C2498 in bacterial 23S rRNA. Mol. Microbiol. 72 (2009) 1147–1158. [PMID: 19400805]
[EC 2.1.1.186 created 2010]
 
 
EC 2.1.1.187     
Accepted name: 23S rRNA (guanine745-N1)-methyltransferase
Reaction: S-adenosyl-L-methionine + guanine745 in 23S rRNA = S-adenosyl-L-homocysteine + N1-methylguanine745 in 23S rRNA
Other name(s): Rlma(I); Rlma1; 23S rRNA m1G745 methyltransferase; YebH; RlmAI methyltransferase; ribosomal RNA(m1G)-methylase (ambiguous); rRNA(m1G)methylase (ambiguous); RrmA (ambiguous); 23S rRNA:m1G745 methyltransferase
Systematic name: S-adenosyl-L-methionine:23S rRNA (guanine745-N1)-methyltransferase
Comments: The enzyme specifically methylates guanine745 at N1 in 23S rRNA.
References:
1.  Liu, M., Novotny, G.W. and Douthwaite, S. Methylation of 23S rRNA nucleotide G745 is a secondary function of the RlmAI methyltransferase. RNA 10 (2004) 1713–1720. [PMID: 15388872]
2.  Gustafsson, C. and Persson, B.C. Identification of the rrmA gene encoding the 23S rRNA m1G745 methyltransferase in Escherichia coli and characterization of an m1G745-deficient mutant. J. Bacteriol. 180 (1998) 359–365. [PMID: 9440525]
3.  Das, K., Acton, T., Chiang, Y., Shih, L., Arnold, E. and Montelione, G.T. Crystal structure of RlmAI: implications for understanding the 23S rRNA G745/G748-methylation at the macrolide antibiotic-binding site. Proc. Natl. Acad. Sci. USA 101 (2004) 4041–4046. [PMID: 14999102]
4.  Hansen, L.H., Kirpekar, F. and Douthwaite, S. Recognition of nucleotide G745 in 23 S ribosomal RNA by the rrmA methyltransferase. J. Mol. Biol. 310 (2001) 1001–1010. [PMID: 11501991]
5.  Liu, M. and Douthwaite, S. Methylation at nucleotide G745 or G748 in 23S rRNA distinguishes Gram-negative from Gram-positive bacteria. Mol. Microbiol. 44 (2002) 195–204. [PMID: 11967079]
[EC 2.1.1.187 created 1976 as EC 2.1.1.51, part transferred 2010 to EC 2.1.1.187]
 
 
EC 2.1.1.188     
Accepted name: 23S rRNA (guanine748-N1)-methyltransferase
Reaction: S-adenosyl-L-methionine + guanine748 in 23S rRNA = S-adenosyl-L-homocysteine + N1-methylguanine748 in 23S rRNA
Other name(s): Rlma(II); Rlma2; 23S rRNA m1G748 methyltransferase; RlmaII; Rlma II; tylosin-resistance methyltransferase RlmA(II); TlrB; rRNA large subunit methyltransferase II
Systematic name: S-adenosyl-L-methionine:23S rRNA (guanine748-N1)-methyltransferase
Comments: The enzyme specifically methylates guanine748 at N1 in 23S rRNA. The methyltransferase RlmAII confers resistance to the macrolide antibiotic tylosin in the drug-producing strain Streptomyces fradiae [1].
References:
1.  Douthwaite, S., Crain, P.F., Liu, M. and Poehlsgaard, J. The tylosin-resistance methyltransferase RlmAII (TlrB) modifies the N-1 position of 23S rRNA nucleotide G748. J. Mol. Biol. 337 (2004) 1073–1077. [PMID: 15046978]
2.  Liu, M., Kirpekar, F., Van Wezel, G.P. and Douthwaite, S. The tylosin resistance gene tlrB of Streptomyces fradiae encodes a methyltransferase that targets G748 in 23S rRNA. Mol. Microbiol. 37 (2000) 811–820. [PMID: 10972803]
3.  Lebars, I., Yoshizawa, S., Stenholm, A.R., Guittet, E., Douthwaite, S. and Fourmy, D. Structure of 23S rRNA hairpin 35 and its interaction with the tylosin-resistance methyltransferase RlmAII. EMBO J. 22 (2003) 183–192. [PMID: 12514124]
4.  Lebars, I., Husson, C., Yoshizawa, S., Douthwaite, S. and Fourmy, D. Recognition elements in rRNA for the tylosin resistance methyltransferase RlmAII. J. Mol. Biol. 372 (2007) 525–534. [PMID: 17673230]
5.  Douthwaite, S., Jakobsen, L., Yoshizawa, S. and Fourmy, D. Interaction of the tylosin-resistance methyltransferase RlmAII at its rRNA target differs from the orthologue RlmAI. J. Mol. Biol. 378 (2008) 969–975. [PMID: 18406425]
6.  Liu, M. and Douthwaite, S. Methylation at nucleotide G745 or G748 in 23S rRNA distinguishes Gram-negative from Gram-positive bacteria. Mol. Microbiol. 44 (2002) 195–204. [PMID: 11967079]
[EC 2.1.1.188 created 1976 as EC 2.1.1.51, part transferred 2010 to EC 2.1.1.188]
 
 
EC 2.1.1.189     
Accepted name: 23S rRNA (uracil747-C5)-methyltransferase
Reaction: S-adenosyl-L-methionine + uracil747 in 23S rRNA = S-adenosyl-L-homocysteine + 5-methyluracil747 in 23S rRNA
Other name(s): YbjF; RumB; RNA uridine methyltransferase B
Systematic name: S-adenosyl-L-methionine:23S rRNA (uracil747-C5)-methyltransferase
Comments: The enzyme specifically methylates uracil747 at C5 in 23S rRNA.
References:
1.  Madsen, C.T., Mengel-Jorgensen, J., Kirpekar, F. and Douthwaite, S. Identifying the methyltransferases for m5U747 and m5U1939 in 23S rRNA using MALDI mass spectrometry. Nucleic Acids Res. 31 (2003) 4738–4746. [PMID: 12907714]
[EC 2.1.1.189 created 2010]
 
 
EC 2.1.1.190     
Accepted name: 23S rRNA (uracil1939-C5)-methyltransferase
Reaction: S-adenosyl-L-methionine + uracil1939 in 23S rRNA = S-adenosyl-L-homocysteine + 5-methyluracil1939 in 23S rRNA
Other name(s): RumA; RNA uridine methyltransferase A; YgcA
Systematic name: S-adenosyl-L-methionine:23S rRNA (uracil1939-C5)-methyltransferase
Comments: The enzyme specifically methylates uracil1939 at C5 in 23S rRNA [1]. The enzyme contains an [4Fe-4S] cluster coordinated by four conserved cysteine residues [2].
References:
1.  Agarwalla, S., Kealey, J.T., Santi, D.V. and Stroud, R.M. Characterization of the 23 S ribosomal RNA m5U1939 methyltransferase from Escherichia coli. J. Biol. Chem. 277 (2002) 8835–8840. [PMID: 11779873]
2.  Lee, T.T., Agarwalla, S. and Stroud, R.M. Crystal structure of RumA, an iron-sulfur cluster containing E. coli ribosomal RNA 5-methyluridine methyltransferase. Structure 12 (2004) 397–407. [PMID: 15016356]
3.  Madsen, C.T., Mengel-Jorgensen, J., Kirpekar, F. and Douthwaite, S. Identifying the methyltransferases for m5U747 and m5U1939 in 23S rRNA using MALDI mass spectrometry. Nucleic Acids Res. 31 (2003) 4738–4746. [PMID: 12907714]
4.  Persaud, C., Lu, Y., Vila-Sanjurjo, A., Campbell, J.L., Finley, J. and O'Connor, M. Mutagenesis of the modified bases, m5U1939 and Ψ2504, in Escherichia coli 23S rRNA. Biochem. Biophys. Res. Commun. 392 (2010) 223–227. [PMID: 20067766]
5.  Agarwalla, S., Stroud, R.M. and Gaffney, B.J. Redox reactions of the iron-sulfur cluster in a ribosomal RNA methyltransferase, RumA: optical and EPR studies. J. Biol. Chem. 279 (2004) 34123–34129. [PMID: 15181002]
6.  Lee, T.T., Agarwalla, S. and Stroud, R.M. A unique RNA Fold in the RumA-RNA-cofactor ternary complex contributes to substrate selectivity and enzymatic function. Cell 120 (2005) 599–611. [PMID: 15766524]
[EC 2.1.1.190 created 2010]
 
 
EC 2.1.1.191     
Accepted name: 23S rRNA (cytosine1962-C5)-methyltransferase
Reaction: S-adenosyl-L-methionine + cytosine1962 in 23S rRNA = S-adenosyl-L-homocysteine + 5-methylcytosine1962 in 23S rRNA
Other name(s): RlmI; rRNA large subunit methyltransferase I; YccW
Systematic name: S-adenosyl-L-methionine:23S rRNA (cytosine1962-C5)-methyltransferase
Comments: The enzyme specifically methylates cytosine1962 at C5 in 23S rRNA.
References:
1.  Purta, E., O'Connor, M., Bujnicki, J.M. and Douthwaite, S. YccW is the m5C methyltransferase specific for 23S rRNA nucleotide 1962. J. Mol. Biol. 383 (2008) 641–651. [PMID: 18786544]
2.  Sunita, S., Tkaczuk, K.L., Purta, E., Kasprzak, J.M., Douthwaite, S., Bujnicki, J.M. and Sivaraman, J. Crystal structure of the Escherichia coli 23S rRNA:m5C methyltransferase RlmI (YccW) reveals evolutionary links between RNA modification enzymes. J. Mol. Biol. 383 (2008) 652–666. [PMID: 18789337]
[EC 2.1.1.191 created 2010]
 
 
EC 2.1.1.192     
Accepted name: 23S rRNA (adenine2503-C2)-methyltransferase
Reaction: (1) 2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin = S-adenosyl-L-homocysteine + L-methionine + 5′-deoxyadenosine + 2-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
(2) 2 S-adenosyl-L-methionine + adenine37 in tRNA + 2 reduced [2Fe-2S] ferredoxin = S-adenosyl-L-homocysteine + L-methionine + 5′-deoxyadenosine + 2-methyladenine37 in tRNA + 2 oxidized [2Fe-2S] ferredoxin
Other name(s): RlmN; YfgB; Cfr
Systematic name: S-adenosyl-L-methionine:23S rRNA (adenine2503-C2)-methyltransferase
Comments: Contains an [4Fe-4S] cluster [2]. This enzyme is a member of the ’AdoMet radical’ (radical SAM) family. S-Adenosyl-L-methionine acts as both a radical generator and as the source of the appended methyl group. RlmN first transfers an CH2 group to a conserved cysteine (Cys355 in Escherichia coli) [6], the generated radical from a second S-adenosyl-L-methionine then attacks the methyl group, exctracting a hydrogen. The formed radical forms a covalent intermediate with the adenine group of the tRNA [9]. RlmN is an endogenous enzyme used by the cell to refine functions of the ribosome in protein synthesis [2]. The enzyme methylates adenosine by a radical mechanism with CH2 from the S-adenosyl-L-methionine and retention of the hydrogen at C-2 of adenosine2503 of 23S rRNA. It will also methylate 8-methyladenosine2503 of 23S rRNA. cf. EC 2.1.1.224 [23S rRNA (adenine2503-C8)-methyltransferase].
References:
1.  Toh, S.M., Xiong, L., Bae, T. and Mankin, A.S. The methyltransferase YfgB/RlmN is responsible for modification of adenosine 2503 in 23S rRNA. RNA 14 (2008) 98–106. [PMID: 18025251]
2.  Yan, F., LaMarre, J.M., Röhrich, R., Wiesner, J., Jomaa, H., Mankin, A.S. and Fujimori, D.G. RlmN and Cfr are radical SAM enzymes involved in methylation of ribosomal RNA. J. Am. Chem. Soc. 132 (2010) 3953–3964. [PMID: 20184321]
3.  Yan, F. and Fujimori, D.G. RNA methylation by radical SAM enzymes RlmN and Cfr proceeds via methylene transfer and hydride shift. Proc. Natl. Acad. Sci. USA 108 (2011) 3930–3934. [PMID: 21368151]
4.  Grove, T.L., Benner, J.S., Radle, M.I., Ahlum, J.H., Landgraf, B.J., Krebs, C. and Booker, S.J. A radically different mechanism for S-adenosylmethionine-dependent methyltransferases. Science 332 (2011) 604–607. [PMID: 21415317]
5.  Boal, A.K., Grove, T.L., McLaughlin, M.I., Yennawar, N.H., Booker, S.J. and Rosenzweig, A.C. Structural basis for methyl transfer by a radical SAM enzyme. Science 332 (2011) 1089–1092. [PMID: 21527678]
6.  Grove, T.L., Radle, M.I., Krebs, C. and Booker, S.J. Cfr and RlmN contain a single [4Fe-4S] cluster, which directs two distinct reactivities for S-adenosylmethionine: methyl transfer by SN2 displacement and radical generation. J. Am. Chem. Soc. 133 (2011) 19586–19589. [PMID: 21916495]
7.  McCusker, K.P., Medzihradszky, K.F., Shiver, A.L., Nichols, R.J., Yan, F., Maltby, D.A., Gross, C.A. and Fujimori, D.G. Covalent intermediate in the catalytic mechanism of the radical S-adenosyl-L-methionine methyl synthase RlmN trapped by mutagenesis. J. Am. Chem. Soc. 134 (2012) 18074–18081. [PMID: 23088750]
8.  Benitez-Paez, A., Villarroya, M. and Armengod, M.E. The Escherichia coli RlmN methyltransferase is a dual-specificity enzyme that modifies both rRNA and tRNA and controls translational accuracy. RNA 18 (2012) 1783–1795. [PMID: 22891362]
9.  Silakov, A., Grove, T.L., Radle, M.I., Bauerle, M.R., Green, M.T., Rosenzweig, A.C., Boal, A.K. and Booker, S.J. Characterization of a cross-linked protein-nucleic acid substrate radical in the reaction catalyzed by RlmN. J. Am. Chem. Soc. 136 (2014) 8221–8228. [PMID: 24806349]
[EC 2.1.1.192 created 2010, modified 2011, modified 2014]
 
 
EC 2.1.1.193     
Accepted name: 16S rRNA (uracil1498-N3)-methyltransferase
Reaction: S-adenosyl-L-methionine + uracil1498 in 16S rRNA = S-adenosyl-L-homocysteine + N3-methyluracil1498 in 16S rRNA
Other name(s): DUF558 protein; YggJ; RsmE; m3U1498 specific methyltransferase
Systematic name: S-adenosyl-L-methionine:16S rRNA (uracil1498-N3)-methyltransferase
Comments: The enzyme specifically methylates uracil1498 at N3 in 16S rRNA.
References:
1.  Basturea, G.N., Rudd, K.E. and Deutscher, M.P. Identification and characterization of RsmE, the founding member of a new RNA base methyltransferase family. RNA 12 (2006) 426–434. [PMID: 16431987]
2.  Basturea, G.N. and Deutscher, M.P. Substrate specificity and properties of the Escherichia coli 16S rRNA methyltransferase, RsmE. RNA 13 (2007) 1969–1976. [PMID: 17872509]
[EC 2.1.1.193 created 2010]
 
 
EC 2.1.1.194      
Deleted entry: 23S rRNA (adenine2503-C2,C8)-dimethyltransferase. A mixture of EC 2.1.1.192 (23S rRNA (adenine2503-C2)-methyltransferase) and EC 2.1.1.224 (23S rRNA (adenine2503-C8)-methyltransferase)
[EC 2.1.1.194 created 2010, deleted 2011]
 
 
EC 2.1.1.195     
Accepted name: cobalt-precorrin-5B (C1)-methyltransferase
Reaction: cobalt-precorrin-5B + S-adenosyl-L-methionine = cobalt-precorrin-6A + S-adenosyl-L-homocysteine
Glossary: cobalt-precorrin-6A = cobalt-precorrin-6x
Other name(s): cobalt-precorrin-6A synthase; CbiD
Systematic name: S-adenosyl-L-methionine:cobalt-precorrin-5B (C1)-methyltransferase
Comments: This enzyme catalyses the C-1 methylation of cobalt-precorrin-5B in the anaerobic (early cobalt insertion) pathway of adenosylcobalamin biosynthesis.
References:
1.  Roper, J.M., Raux, E., Brindley, A.A., Schubert, H.L., Gharbia, S.E., Shah, H.N. and Warren, M.J. The enigma of cobalamin (Vitamin B12) biosynthesis in Porphyromonas gingivalis. Identification and characterization of a functional corrin pathway. J. Biol. Chem. 275 (2000) 40316–40323. [PMID: 11007789]
2.  Roessner, C.A., Williams, H.J. and Scott, A.I. Genetically engineered production of 1-desmethylcobyrinic acid, 1-desmethylcobyrinic acid a,c-diamide, and cobyrinic acid a,c-diamide in Escherichia coli implies a role for CbiD in C-1 methylation in the anaerobic pathway to cobalamin. J. Biol. Chem. 280 (2005) 16748–16753. [PMID: 15741157]
3.  Moore, S.J., Lawrence, A.D., Biedendieck, R., Deery, E., Frank, S., Howard, M.J., Rigby, S.E. and Warren, M.J. Elucidation of the anaerobic pathway for the corrin component of cobalamin (vitamin B12). Proc. Natl. Acad. Sci. USA 110 (2013) 14906–14911. [PMID: 23922391]
[EC 2.1.1.195 created 2010]
 
 
EC 2.1.1.196     
Accepted name: cobalt-precorrin-6B (C15)-methyltransferase [decarboxylating]
Reaction: cobalt-precorrin-6B + S-adenosyl-L-methionine = cobalt-precorrin-7 + S-adenosyl-L-homocysteine + CO2
Other name(s): cbiT (gene name); S-adenosyl-L-methionine:precorrin-7 C15-methyltransferase (C-12-decarboxylating); cobalt-precorrin-7 (C15)-methyltransferase [decarboxylating]
Systematic name: S-adenosyl-L-methionine:precorrin-6B C15-methyltransferase (C-12-decarboxylating)
Comments: This enzyme catalyses both methylation at C-15 and decarboxylation of the C-12 acetate side chain of cobalt-precorrin-6B, a step in the anaerobic (early cobalt insertion) adenosylcobalamin biosynthesis pathway.
References:
1.  Keller, J.P., Smith, P.M., Benach, J., Christendat, D., deTitta, G.T. and Hunt, J.F. The crystal structure of MT0146/CbiT suggests that the putative precorrin-8w decarboxylase is a methyltransferase. Structure 10 (2002) 1475–1487. [PMID: 12429089]
2.  Santander, P.J., Kajiwara, Y., Williams, H.J. and Scott, A.I. Structural characterization of novel cobalt corrinoids synthesized by enzymes of the vitamin B12 anaerobic pathway. Bioorg. Med. Chem. 14 (2006) 724–731. [PMID: 16198574]
3.  Moore, S.J., Lawrence, A.D., Biedendieck, R., Deery, E., Frank, S., Howard, M.J., Rigby, S.E. and Warren, M.J. Elucidation of the anaerobic pathway for the corrin component of cobalamin (vitamin B12). Proc. Natl. Acad. Sci. USA 110 (2013) 14906–14911. [PMID: 23922391]
[EC 2.1.1.196 created 2010, modified 2013]
 
 
EC 2.1.1.197     
Accepted name: malonyl-[acyl-carrier protein] O-methyltransferase
Reaction: S-adenosyl-L-methionine + malonyl-[acyl-carrier protein] = S-adenosyl-L-homocysteine + malonyl-[acyl-carrier protein] methyl ester
Other name(s): BioC
Systematic name: S-adenosyl-L-methionine:malonyl-[acyl-carrier protein] O-methyltransferase
Comments: Involved in an early step of biotin biosynthesis in Gram-negative bacteria. This enzyme catalyses the transfer of a methyl group to the ω-carboxyl group of malonyl-[acyl-carrier protein] forming a methyl ester. The methyl ester is recognized by the fatty acid synthetic enzymes, which process it via the fatty acid elongation cycle to give pimelyl-[acyl-carrier-protein] methyl ester [5]. While the enzyme can also accept malonyl-CoA, it has a much higher activity with malonyl-[acyl-carrier protein] [6]
References:
1.  Del Campillo-Campbell, A., Kayajanian, G., Campbell, A. and Adhya, S. Biotin-requiring mutants of Escherichia coli K-12. J. Bacteriol. 94 (1967) 2065–2066. [PMID: 4864413]
2.  Rolfe, B. and Eisenberg, M.A. Genetic and biochemical analysis of the biotin loci of Escherichia coli K-12. J. Bacteriol. 96 (1968) 515–524. [PMID: 4877129]
3.  Otsuka, A.J., Buoncristiani, M.R., Howard, P.K., Flamm, J., Johnson, C., Yamamoto, R., Uchida, K., Cook, C., Ruppert, J. and Matsuzaki, J. The Escherichia coli biotin biosynthetic enzyme sequences predicted from the nucleotide sequence of the bio operon. J. Biol. Chem. 263 (1988) 19577–19585. [PMID: 3058702]
4.  Cleary, P.P. and Campbell, A. Deletion and complementation analysis of biotin gene cluster of Escherichia coli. J. Bacteriol. 112 (1972) 830–839. [PMID: 4563978]
5.  Lin, S., Hanson, R.E. and Cronan, J.E. Biotin synthesis begins by hijacking the fatty acid synthetic pathway. Nat. Chem. Biol. 6 (2010) 682–688. [PMID: 20693992]
6.  Lin, S. and Cronan, J.E. The BioC O-methyltransferase catalyzes methyl esterification of malonyl-acyl carrier protein, an essential step in biotin synthesis. J. Biol. Chem. 287 (2012) 37010–37020. [PMID: 22965231]
[EC 2.1.1.197 created 2010, modified 2013]
 
 
EC 2.1.1.198     
Accepted name: 16S rRNA (cytidine1402-2′-O)-methyltransferase
Reaction: S-adenosyl-L-methionine + cytidine1402 in 16S rRNA = S-adenosyl-L-homocysteine + 2′-O-methylcytidine1402 in 16S rRNA
Other name(s): RsmI; YraL
Systematic name: S-adenosyl-L-methionine:16S rRNA (cytidine1402-2′-O)-methyltransferase
Comments: RsmI catalyses the 2′-O-methylation of cytidine1402 and RsmH (EC 2.1.1.199) catalyses the N4-methylation of cytidine1402 in 16S rRNA. Both methylations are necessary for efficient translation initiation at the UUG and GUG codons.
References:
1.  Kimura, S. and Suzuki, T. Fine-tuning of the ribosomal decoding center by conserved methyl-modifications in the Escherichia coli 16S rRNA. Nucleic Acids Res. 38 (2010) 1341–1352. [PMID: 19965768]
[EC 2.1.1.198 created 2010]
 
 
EC 2.1.1.199     
Accepted name: 16S rRNA (cytosine1402-N4)-methyltransferase
Reaction: S-adenosyl-L-methionine + cytosine1402 in 16S rRNA = S-adenosyl-L-homocysteine + N4-methylcytosine1402 in 16S rRNA
Other name(s): RsmH; MraW
Systematic name: S-adenosyl-L-methionine:16S rRNA (cytosine1402-N4)-methyltransferase
Comments: RsmH catalyses the N4-methylation of cytosine1402 and RsmI (EC 2.1.1.198) catalyses the 2′-O-methylation of cytosine1402 in 16S rRNA. Both methylations are necessary for efficient translation initiation at the UUG and GUG codons.
References:
1.  Kimura, S. and Suzuki, T. Fine-tuning of the ribosomal decoding center by conserved methyl-modifications in the Escherichia coli 16S rRNA. Nucleic Acids Res. 38 (2010) 1341–1352. [PMID: 19965768]
[EC 2.1.1.199 created 2010]
 
 
EC 2.1.1.200     
Accepted name: tRNA (cytidine32/uridine32-2′-O)-methyltransferase
Reaction: (1) S-adenosyl-L-methionine + cytidine32 in tRNA = S-adenosyl-L-homocysteine + 2′-O-methylcytidine32 in tRNA
(2) S-adenosyl-L-methionine + uridine32 in tRNA = S-adenosyl-L-homocysteine + 2′-O-methyluridine32 in tRNA
Other name(s): YfhQ; tRNA:Cm32/Um32 methyltransferase; TrMet(Xm32); TrmJ
Systematic name: S-adenosyl-L-methionine:tRNA (cytidine32/uridine32-2′-O)-methyltransferase
Comments: In Escherichia coli YfhQ is the only methyltransferase responsible for the formation of 2′-O-methylcytidine32 in tRNA. No methylation of cytosine34 in tRNALeu(CAA). In vitro the enzyme 2-O-methylates cytidine32 of tRNASer1 and uridine32 of tRNAGln2.
References:
1.  Purta, E., van Vliet, F., Tkaczuk, K.L., Dunin-Horkawicz, S., Mori, H., Droogmans, L. and Bujnicki, J.M. The yfhQ gene of Escherichia coli encodes a tRNA:Cm32/Um32 methyltransferase. BMC Mol. Biol. 7:23 (2006). [PMID: 16848900]
[EC 2.1.1.200 created 2011]
 
 
EC 2.1.1.201     
Accepted name: 2-methoxy-6-polyprenyl-1,4-benzoquinol methylase
Reaction: S-adenosyl-L-methionine + 2-methoxy-6-all-trans-polyprenyl-1,4-benzoquinol = S-adenosyl-L-homocysteine + 6-methoxy-3-methyl-2-all-trans-polyprenyl-1,4-benzoquinol
Other name(s): ubiE (gene name, ambiguous)
Systematic name: S-adenosyl-L-methionine:2-methoxy-6-all-trans-polyprenyl-1,4-benzoquinol 5-C-methyltransferase
Comments: This enzyme is involved in ubiquinone biosynthesis. Ubiquinones from different organisms have a different number of prenyl units (for example, ubiquinone-6 in Saccharomyces, ubiquinone-9 in rat and ubiquinone-10 in human), and thus the natural substrate for the enzymes from different organisms has a different number of prenyl units. However, the enzyme usually shows a low degree of specificity regarding the number of prenyl units. For example, when the COQ5 gene from Saccharomyces cerevisiae is introduced into Escherichia coli, it complements the respiratory deficiency of an ubiE mutant [3]. The bifunctional enzyme from Escherichia coli also catalyses the methylation of demethylmenaquinol-8 (this activity is classified as EC 2.1.1.163) [1].
References:
1.  Lee, P.T., Hsu, A.Y., Ha, H.T. and Clarke, C.F. A C-methyltransferase involved in both ubiquinone and menaquinone biosynthesis: isolation and identification of the Escherichia coli ubiE gene. J. Bacteriol. 179 (1997) 1748–1754. [PMID: 9045837]
2.  Young, I.G., McCann, L.M., Stroobant, P. and Gibson, F. Characterization and genetic analysis of mutant strains of Escherichia coli K-12 accumulating the biquinone precursors 2-octaprenyl-6-methoxy-1,4-benzoquinone and 2-octaprenyl-3-methyl-6-methoxy-1,4-benzoquinone. J. Bacteriol. 105 (1971) 769–778. [PMID: 4323297]
3.  Dibrov, E., Robinson, K.M. and Lemire, B.D. The COQ5 gene encodes a yeast mitochondrial protein necessary for ubiquinone biosynthesis and the assembly of the respiratory chain. J. Biol. Chem. 272 (1997) 9175–9181. [PMID: 9083048]
4.  Barkovich, R.J., Shtanko, A., Shepherd, J.A., Lee, P.T., Myles, D.C., Tzagoloff, A. and Clarke, C.F. Characterization of the COQ5 gene from Saccharomyces cerevisiae. Evidence for a C-methyltransferase in ubiquinone biosynthesis. J. Biol. Chem. 272 (1997) 9182–9188. [PMID: 9083049]
[EC 2.1.1.201 created 2011]
 
 
EC 2.1.1.202     
Accepted name: multisite-specific tRNA:(cytosine-C5)-methyltransferase
Reaction: (1) S-adenosyl-L-methionine + cytosine34 in tRNA precursor = S-adenosyl-L-homocysteine + 5-methylcytosine34 in tRNA precursor
(2) S-adenosyl-L-methionine + cytosine40 in tRNA precursor = S-adenosyl-L-homocysteine + 5-methylcytosine40 in tRNA precursor
(3) S-adenosyl-L-methionine + cytosine48 in tRNA = S-adenosyl-L-homocysteine + 5-methylcytosine48 in tRNA
(4) S-adenosyl-L-methionine + cytosine49 in tRNA = S-adenosyl-L-homocysteine + 5-methylcytosine49 in tRNA
Other name(s): multisite-specific tRNA:m5C-methyltransferase; TRM4 (gene name, gene corresponding to ORF YBL024w)
Systematic name: S-adenosyl-L-methionine:tRNA (cytosine-C5)-methyltransferase
Comments: The enzyme from Saccharomyces cerevisiae is responsible for complete 5-methylcytosine methylations of yeast tRNA. The incidence of modification depends on the cytosine position in tRNA. At positions 34 and 40, 5-methylcytosine is found only in two yeast tRNAs (tRNALeu(CUA) and tRNAPhe(GAA), respectively), whereas most other elongator yeast tRNAs bear either 5-methylcytosine48 or 5-methylcytosine49, but never both in the same tRNA molecule [1]. The formation of 5-methylcytosine34 and 5-methylcytosine40 is a strictly intron-dependent process, whereas the formation of 5-methylcytosine48 and 5-methylcytosine49 is an intron-independent process [2,3].
References:
1.  Motorin, Y. and Grosjean, H. Multisite-specific tRNA:m5C-methyltransferase (Trm4) in yeast Saccharomyces cerevisiae: identification of the gene and substrate specificity of the enzyme. RNA 5 (1999) 1105–1118. [PMID: 10445884]
2.  Jiang, H.Q., Motorin, Y., Jin, Y.X. and Grosjean, H. Pleiotropic effects of intron removal on base modification pattern of yeast tRNAPhe: an in vitro study. Nucleic Acids Res. 25 (1997) 2694–2701. [PMID: 9207014]
3.  Strobel, M.C. and Abelson, J. Effect of intron mutations on processing and function of Saccharomyces cerevisiae SUP53 tRNA in vitro and in vivo. Mol. Cell Biol. 6 (1986) 2663–2673. [PMID: 3537724]
4.  Walbott, H., Husson, C., Auxilien, S. and Golinelli-Pimpaneau, B. Cysteine of sequence motif VI is essential for nucleophilic catalysis by yeast tRNA m5C methyltransferase. RNA 13 (2007) 967–973. [PMID: 17475914]
[EC 2.1.1.202 created 1976 as EC 2.1.1.29, part transferred 2011 to EC 2.1.1.202]
 
 
EC 2.1.1.203     
Accepted name: tRNA (cytosine34-C5)-methyltransferase
Reaction: S-adenosyl-L-methionine + cytosine34 in tRNA precursor = S-adenosyl-L-homocysteine + 5-methylcytosine34 in tRNA precursor
Other name(s): hTrm4 Mtase; hTrm4 methyltransferase; hTrm4 (gene name); tRNA:m5C-methyltransferase (ambiguous)
Systematic name: S-adenosyl-L-methionine:tRNA (cytosine34-C5)-methyltransferase
Comments: The human enzyme is specific for C5-methylation of cytosine34 in tRNA precursors. The intron in the human pre-tRNALeu(CAA) is indispensable for the C5-methylation of cytosine in the first position of the anticodon. It is not able to form 5-methylcytosine at positions 48 and 49 of human and yeast tRNA precursors [1].
References:
1.  Brzezicha, B., Schmidt, M., Makalowska, I., Jarmolowski, A., Pienkowska, J. and Szweykowska-Kulinska, Z. Identification of human tRNA:m5C methyltransferase catalysing intron-dependent m5C formation in the first position of the anticodon of the pre-tRNA Leu (CAA). Nucleic Acids Res. 34 (2006) 6034–6043. [PMID: 17071714]
[EC 2.1.1.203 created 1976 as EC 2.1.1.29, part transferred 2011 to EC 2.1.1.203]
 
 
EC 2.1.1.204     
Accepted name: tRNA (cytosine38-C5)-methyltransferase
Reaction: S-adenosyl-L-methionine + cytosine38 in tRNA = S-adenosyl-L-homocysteine + 5-methylcytosine38 in tRNA
Other name(s): hDNMT2 (gene name); DNMT2 (gene name); TRDMT1 (gene name)
Systematic name: S-adenosyl-L-methionine:tRNA (cytosine38-C5)-methyltransferase
Comments: The eukaryotic enzyme catalyses methylation of cytosine38 in the anti-codon loop of tRNAAsp(GTC), tRNAVal(AAC) and tRNAGly(GCC). Methylation by Dnmt2 protects tRNAs against stress-induced cleavage by ribonuclease [3].
References:
1.  Goll, M.G., Kirpekar, F., Maggert, K.A., Yoder, J.A., Hsieh, C.L., Zhang, X., Golic, K.G., Jacobsen, S.E. and Bestor, T.H. Methylation of tRNAAsp by the DNA methyltransferase homolog Dnmt2. Science 311 (2006) 395–398. [PMID: 16424344]
2.  Jurkowski, T.P., Meusburger, M., Phalke, S., Helm, M., Nellen, W., Reuter, G. and Jeltsch, A. Human DNMT2 methylates tRNA(Asp) molecules using a DNA methyltransferase-like catalytic mechanism. RNA 14 (2008) 1663–1670. [PMID: 18567810]
3.  Schaefer, M., Pollex, T., Hanna, K., Tuorto, F., Meusburger, M., Helm, M. and Lyko, F. RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage. Genes Dev. 24 (2010) 1590–1595. [PMID: 20679393]
[EC 2.1.1.204 created 1976 as EC 2.1.1.29, part transferred 2011 to EC 2.1.1.204]
 
 
EC 2.1.1.205     
Accepted name: tRNA (cytidine32/guanosine34-2′-O)-methyltransferase
Reaction: S-adenosyl-L-methionine + cytidine32/guanosine34 in tRNA = S-adenosyl-L-homocysteine + 2′-O-methylcytidine32/2′-O-methylguanosine34 in tRNA
Other name(s): Trm7p
Systematic name: S-adenosyl-L-methionine:tRNA (cytidine32/guanosine34-2′-O)-methyltransferase
Comments: The enzyme from Saccharomyces cerevisiae catalyses the formation of 2′-O-methylnucleotides at positions 32 and 34 of the yeast tRNAPhe, tRNATrp and, possibly, tRNALeu.
References:
1.  Pintard, L., Lecointe, F., Bujnicki, J.M., Bonnerot, C., Grosjean, H. and Lapeyre, B. Trm7p catalyses the formation of two 2′-O-methylriboses in yeast tRNA anticodon loop. EMBO J. 21 (2002) 1811–1820. [PMID: 11927565]
[EC 2.1.1.205 created 2011]
 
 
EC 2.1.1.206     
Accepted name: tRNA (cytidine56-2′-O)-methyltransferase
Reaction: S-adenosyl-L-methionine + cytidine56 in tRNA = S-adenosyl-L-homocysteine + 2′-O-methylcytidine56 in tRNA
Other name(s): aTrm56; tRNA ribose 2′-O-methyltransferase aTrm56; PAB1040 (gene name)
Systematic name: S-adenosyl-L-methionine:tRNA (cytidine56-2′-O)-methyltransferase
Comments: The archaeal enzyme specifically catalyses the S-adenosyl-L-methionine dependent 2′-O-ribose methylation of cytidine at position 56 in tRNA transcripts.
References:
1.  Renalier, M.H., Joseph, N., Gaspin, C., Thebault, P. and Mougin, A. The Cm56 tRNA modification in archaea is catalyzed either by a specific 2′-O-methylase, or a C/D sRNP. RNA 11 (2005) 1051–1063. [PMID: 15987815]
2.  Kuratani, M., Bessho, Y., Nishimoto, M., Grosjean, H. and Yokoyama, S. Crystal structure and mutational study of a unique SpoU family archaeal methylase that forms 2′-O-methylcytidine at position 56 of tRNA. J. Mol. Biol. 375 (2008) 1064–1075. [PMID: 18068186]
[EC 2.1.1.206 created 2011]
 
 
EC 2.1.1.207     
Accepted name: tRNA (cytidine34-2′-O)-methyltransferase
Reaction: (1) S-adenosyl-L-methionine + cytidine34 in tRNA = S-adenosyl-L-homocysteine + 2′-O-methylcytidine34 in tRNA
(2) S-adenosyl-L-methionine + 5-carboxymethylaminomethyluridine34 in tRNALeu = S-adenosyl-L-homocysteine + 5-carboxymethylaminomethyl-2′-O-methyluridine34 in tRNALeu
Other name(s): yibK (gene name); methyltransferase yibK; TrmL; tRNA methyltransferase L; tRNA (cytidine34/5-carboxymethylaminomethyluridine34-2′-O)-methyltransferase
Systematic name: S-adenosyl-L-methionine:tRNA (cytidine34/5-carboxymethylaminomethyluridine34-2′-O)-methyltransferase
Comments: The enzyme from Escherichia coli catalyses the 2′-O-methylation of cytidine or 5-carboxymethylaminomethyluridine at the wobble position at nucleotide 34 in tRNALeuCmAA and tRNALeucmnm5UmAA. The enzyme is selective for the two tRNALeu isoacceptors and only methylates these when they present the correct anticodon loop sequence and modification pattern. Specifically, YibK requires a pyrimidine nucleoside at position 34, it has a clear preference for an adenosine at position 35, and it fails to methylate without prior addition of the N6-(isopentenyl)-2-methylthioadenosine modification at position 37.
References:
1.  Benitez-Paez, A., Villarroya, M., Douthwaite, S., Gabaldon, T. and Armengod, M.E. YibK is the 2′-O-methyltransferase TrmL that modifies the wobble nucleotide in Escherichia coli tRNA(Leu) isoacceptors. RNA 16 (2010) 2131–2143. [PMID: 20855540]
[EC 2.1.1.207 created 2011]
 
 
EC 2.1.1.208     
Accepted name: 23S rRNA (uridine2479-2′-O)-methyltransferase
Reaction: S-adenosyl-L-methionine + uridine2479 in 23S rRNA = S-adenosyl-L-homocysteine + 2′-O-methyluridine2479 in 23S rRNA
Other name(s): AviRb
Systematic name: S-adenosyl-L-methionine:23S rRNA (uridine2479-2′-O)-methyltransferase
Comments: Streptomyces viridochromogenes produces the antibiotic avilamycin A which binds to the 50S ribosomal subunit to inhibit protein synthesis. To protect itself from the antibiotic, Streptomyces viridochromogenes utilizes two methyltransferases, 23S rRNA (uridine2479-2′-O)-methyltransferase and EC 2.1.1.209 [23S rRNA (guanine2535-N1)-methyltransferase], whose actions confer avilamycin resistance to the RNA.
References:
1.  Mosbacher, T.G., Bechthold, A. and Schulz, G.E. Structure and function of the antibiotic resistance-mediating methyltransferase AviRb from Streptomyces viridochromogenes. J. Mol. Biol. 345 (2005) 535–545. [PMID: 15581897]
2.  Treede, I., Jakobsen, L., Kirpekar, F., Vester, B., Weitnauer, G., Bechthold, A. and Douthwaite, S. The avilamycin resistance determinants AviRa and AviRb methylate 23S rRNA at the guanosine 2535 base and the uridine 2479 ribose. Mol. Microbiol. 49 (2003) 309–318. [PMID: 12828631]
3.  Weitnauer, G., Gaisser, S., Trefzer, A., Stockert, S., Westrich, L., Quiros, L.M., Mendez, C., Salas, J.A. and Bechthold, A. An ATP-binding cassette transporter and two rRNA methyltransferases are involved in resistance to avilamycin in the producer organism Streptomyces viridochromogenes Tu57. Antimicrob. Agents Chemother. 45 (2001) 690–695. [PMID: 11181344]
[EC 2.1.1.208 created 2011]
 
 
EC 2.1.1.209     
Accepted name: 23S rRNA (guanine2535-N1)-methyltransferase
Reaction: S-adenosyl-L-methionine + guanine2535 in 23S rRNA = S-adenosyl-L-homocysteine + N1-methylguanine2535 in 23S rRNA
Other name(s): AviRa
Systematic name: S-adenosyl-L-methionine:23S rRNA (guanine2535-N1)-methyltransferase
Comments: Streptomyces viridochromogenes produces the antibiotic avilamycin A which binds to the 50S ribosomal subunit to inhibit protein synthesis. To protect itself from the antibiotic, Streptomyces viridochromogenes utilizes two methyltransferases, 23S rRNA (guanine2535-N1)-methyltransferase and EC 2.1.1.208 [23S rRNA (uridine2479-2-O)-methyltransferase], whose actions confer avilamycin resistance to the RNA.
References:
1.  Treede, I., Jakobsen, L., Kirpekar, F., Vester, B., Weitnauer, G., Bechthold, A. and Douthwaite, S. The avilamycin resistance determinants AviRa and AviRb methylate 23S rRNA at the guanosine 2535 base and the uridine 2479 ribose. Mol. Microbiol. 49 (2003) 309–318. [PMID: 12828631]
2.  Weitnauer, G., Gaisser, S., Trefzer, A., Stockert, S., Westrich, L., Quiros, L.M., Mendez, C., Salas, J.A. and Bechthold, A. An ATP-binding cassette transporter and two rRNA methyltransferases are involved in resistance to avilamycin in the producer organism Streptomyces viridochromogenes Tu57. Antimicrob. Agents Chemother. 45 (2001) 690–695. [PMID: 11181344]
3.  Mosbacher, T.G., Bechthold, A. and Schulz, G.E. Crystal structure of the avilamycin resistance-conferring methyltransferase AviRa from Streptomyces viridochromogenes. J. Mol. Biol. 329 (2003) 147–157. [PMID: 12742024]
[EC 2.1.1.209 created 2011]
 
 
EC 2.1.1.210     
Accepted name: demethylspheroidene O-methyltransferase
Reaction: S-adenosyl-L-methionine + demethylspheroidene = S-adenosyl-L-homocysteine + spheroidene
Other name(s): 1-hydroxycarotenoid O-methylase; 1-hydroxycarotenoid methylase; 1-HO-carotenoid methylase; CrtF
Systematic name: S-adenosyl-L-methionine:demethylspheroidene O-methyltransferase
Comments: In Rhodopseudomonas capsulata and Rubrivivax gelatinosus the enzyme is involved in biosynthesis of spheroidene [1,2,3]. In Rubrivivax gelatinosus the enzyme also catalyses the methylation of demethylspirilloxanthin to spirilloxanthin and the methylation of 3,4-didehydrorhodopin to anhydrorhodovibrin [2].
References:
1.  Badenhop, F., Steiger, S., Sandmann, M. and Sandmann, G. Expression and biochemical characterization of the 1-HO-carotenoid methylase CrtF from Rhodobacter capsulatus. FEMS Microbiol. Lett. 222 (2003) 237–242. [PMID: 12770713]
2.  Pinta, V., Ouchane, S., Picaud, M., Takaichi, S., Astier, C. and Reiss-Husson, F. Characterization of unusual hydroxy- and ketocarotenoids in Rubrivivax gelatinosus: involvement of enzyme CrtF or CrtA. Arch. Microbiol. 179 (2003) 354–362. [PMID: 12664193]
3.  Scolnik, P.A., Walker, M.A. and Marrs, B.L. Biosynthesis of carotenoids derived from neurosporene in Rhodopseudomonas capsulata. J. Biol. Chem. 255 (1980) 2427–2432. [PMID: 7358679]
[EC 2.1.1.210 created 2011]
 
 
EC 2.1.1.211     
Accepted name: tRNASer (uridine44-2′-O)-methyltransferase
Reaction: S-adenosyl-L-methionine + uridine44 in tRNASer = S-adenosyl-L-homocysteine + 2′-O-methyluridine44 in tRNASer
Other name(s): TRM44
Systematic name: S-adenosyl-L-methionine:tRNASer (uridine44-2′-O)-methyltransferase
Comments: The 2′-O-methylation of uridine44 contributes to stability of tRNASer(CGA).
References:
1.  Kotelawala, L., Grayhack, E.J. and Phizicky, E.M. Identification of yeast tRNA Um44 2′-O-methyltransferase (Trm44) and demonstration of a Trm44 role in sustaining levels of specific tRNASer species. RNA 14 (2008) 158–169. [PMID: 18025252]
[EC 2.1.1.211 created 2011]
 
 
EC 2.1.1.212     
Accepted name: 2,7,4′-trihydroxyisoflavanone 4′-O-methyltransferase
Reaction: S-adenosyl-L-methionine + 2,4′,7-trihydroxyisoflavanone = S-adenosyl-L-homocysteine + 2,7-dihydroxy-4′-methoxyisoflavanone
Other name(s): SAM:2,7,4′-trihydroxyisoflavanone 4′-O-methyltransferase; HI4′OMT; HMM1; MtIOMT5; S-adenosyl-L-methionine:2,7,4′-trihydroxyisoflavanone 4′-O-methyltransferase
Systematic name: S-adenosyl-L-methionine:2,4′,7-trihydroxyisoflavanone 4′-O-methyltransferase
Comments: Specifically methylates 2,4′,7-trihydroxyisoflavanone on the 4′-position. No activity with isoflavones [2]. The enzyme is involved in formononetin biosynthesis in legumes [1]. The protein from pea (Pisum sativum) also methylates (+)-6a-hydroxymaackiain at the 3-position (cf. EC 2.1.1.270, (+)-6a-hydroxymaackiain 3-O-methyltransferase) [4].
References:
1.  Akashi, T., Sawada, Y., Shimada, N., Sakurai, N., Aoki, T. and Ayabe, S. cDNA cloning and biochemical characterization of S-adenosyl-L-methionine: 2,7,4′-trihydroxyisoflavanone 4′-O-methyltransferase, a critical enzyme of the legume isoflavonoid phytoalexin pathway. Plant Cell Physiol. 44 (2003) 103–112. [PMID: 12610212]
2.  Deavours, B.E., Liu, C.J., Naoumkina, M.A., Tang, Y., Farag, M.A., Sumner, L.W., Noel, J.P. and Dixon, R.A. Functional analysis of members of the isoflavone and isoflavanone O-methyltransferase enzyme families from the model legume Medicago truncatula. Plant Mol. Biol. 62 (2006) 715–733. [PMID: 17001495]
3.  Liu, C.J., Deavours, B.E., Richard, S.B., Ferrer, J.L., Blount, J.W., Huhman, D., Dixon, R.A. and Noel, J.P. Structural basis for dual functionality of isoflavonoid O-methyltransferases in the evolution of plant defense responses. Plant Cell 18 (2006) 3656–3669. [PMID: 17172354]
4.  Akashi, T., VanEtten, H.D., Sawada, Y., Wasmann, C.C., Uchiyama, H. and Ayabe, S. Catalytic specificity of pea O-methyltransferases suggests gene duplication for (+)-pisatin biosynthesis. Phytochemistry 67 (2006) 2525–2530. [PMID: 17067644]
[EC 2.1.1.212 created 2011]
 
 
EC 2.1.1.213     
Accepted name: tRNA (guanine10-N2)-dimethyltransferase
Reaction: 2 S-adenosyl-L-methionine + guanine10 in tRNA = 2 S-adenosyl-L-homocysteine + N2-dimethylguanine10 in tRNA (overall reaction)
(1a) S-adenosyl-L-methionine + guanine10 in tRNA = S-adenosyl-L-homocysteine + N2-methylguanine10 in tRNA
(1b) S-adenosyl-L-methionine + N2-methylguanine10 in tRNA = S-adenosyl-L-homocysteine + N2-dimethylguanine10 in tRNA
Other name(s): PAB1283; N(2),N(2)-dimethylguanosine tRNA methyltransferase; Trm-G10; PabTrm-G10; PabTrm-m2 2G10 enzyme
Systematic name: S-adenosyl-L-methionine:tRNA (guanine10-N2)-dimethyltransferase
References:
1.  Armengaud, J., Urbonavicius, J., Fernandez, B., Chaussinand, G., Bujnicki, J.M. and Grosjean, H. N2-Methylation of guanosine at position 10 in tRNA is catalyzed by a THUMP domain-containing, S-adenosylmethionine-dependent methyltransferase, conserved in Archaea and Eukaryota. J. Biol. Chem. 279 (2004) 37142–37152. [PMID: 15210688]
[EC 2.1.1.213 created 2011 (EC 2.1.1.32 created 1972, part transferred 2011 to EC 2.1.1.213)]
 
 
EC 2.1.1.214     
Accepted name: tRNA (guanine10-N2)-methyltransferase
Reaction: S-adenosyl-L-methionine + guanine10 in tRNA = S-adenosyl-L-homocysteine + N2-methylguanine10 in tRNA
Other name(s): (m2G10) methyltransferase; Trm11-Trm112 complex
Systematic name: S-adenosyl-L-methionine:tRNA (guanine10-N2)-methyltransferase
Comments: In contrast to the archaeal enzyme tRNA (guanine10-N2)-dimethyltransferase (EC 2.1.1.213), tRNA (guanine10-N2)-methyltransferase from yeast does not catalyse the methylation from N2-methylguanine10 to N2-dimethylguanine10 in tRNA.
References:
1.  Purushothaman, S.K., Bujnicki, J.M., Grosjean, H. and Lapeyre, B. Trm11p and Trm112p are both required for the formation of 2-methylguanosine at position 10 in yeast tRNA. Mol. Cell Biol. 25 (2005) 4359–4370. [PMID: 15899842]
[EC 2.1.1.214 created 2011 (EC 2.1.1.32 created 1972, part transferred 2011 to EC 2.1.1.214)]
 
 
EC 2.1.1.215     
Accepted name: tRNA (guanine26-N2/guanine27-N2)-dimethyltransferase
Reaction: 4 S-adenosyl-L-methionine + guanine26/guanine27 in tRNA = 4 S-adenosyl-L-homocysteine + N2-dimethylguanine26/N2-dimethylguanine27 in tRNA
Other name(s): Trm1 (ambiguous); tRNA (N2,N2-guanine)-dimethyltransferase; tRNA (m2(2G26) methyltransferase; Trm1[tRNA (m2(2)G26) methyltransferase]
Systematic name: S-adenosyl-L-methionine:tRNA (guanine26-N2/guanine27-N2)-dimethyltransferase
Comments: The enzyme from Aquifex aeolicus is similar to the TRM1 methyltransferases of archaea and eukarya (see EC 2.1.1.216, tRNA (guanine26-N2)-dimethyltransferase). However, it catalyses the double methylation of guanines at both positions 26 and 27 of tRNA.
References:
1.  Awai, T., Kimura, S., Tomikawa, C., Ochi, A., Ihsanawati, Bessho, Y., Yokoyama, S., Ohno, S., Nishikawa, K., Yokogawa, T., Suzuki, T. and Hori, H. Aquifex aeolicus tRNA (N2,N2-guanine)-dimethyltransferase (Trm1) catalyzes transfer of methyl groups not only to guanine 26 but also to guanine 27 in tRNA. J. Biol. Chem. 284 (2009) 20467–20478. [PMID: 19491098]
[EC 2.1.1.215 created 2011 (EC 2.1.1.32 created 1972, part transferred 2011 to EC 2.1.1.215)]
 
 
EC 2.1.1.216     
Accepted name: tRNA (guanine26-N2)-dimethyltransferase
Reaction: 2 S-adenosyl-L-methionine + guanine26 in tRNA = 2 S-adenosyl-L-homocysteine + N2-dimethylguanine26 in tRNA
Other name(s): Trm1p; TRM1; tRNA (m22G26)dimethyltransferase
Systematic name: S-adenosyl-L-methionine:tRNA (guanine26-N2)-dimethyltransferase
Comments: The enzyme dissociates from its tRNA substrate between the two consecutive methylation reactions. In contrast to EC 2.1.1.215, tRNA (guanine26-N2/guanine27-N2)-dimethyltransferase, this enzyme does not catalyse the methylation of guanine27 in tRNA.
References:
1.  Constantinesco, F., Motorin, Y. and Grosjean, H. Characterisation and enzymatic properties of tRNA(guanine26, N2,N2-dimethyltransferase (Trm1p) from Pyrococcus furiosus. J. Mol. Biol. 291 (1999) 375–392. [PMID: 10438627]
2.  Constantinesco, F., Benachenhou, N., Motorin, Y. and Grosjean, H. The tRNA(guanine-26,N2-N2) methyltransferase (Trm1) from the hyperthermophilic archaeon Pyrococcus furiosus: cloning, sequencing of the gene and its expression in Escherichia coli. Nucleic Acids Res. 26 (1998) 3753–3761. [PMID: 9685492]
3.  Liu, J., Liu, J. and Straby, K.B. Point and deletion mutations eliminate one or both methyl group transfers catalysed by the yeast TRM1 encoded tRNA (m22G26)dimethyltransferase. Nucleic Acids Res. 26 (1998) 5102–5108. [PMID: 9801306]
4.  Liu, J., Zhou, G.Q. and Straby, K.B. Caenorhabditis elegans ZC376.5 encodes a tRNA (m22G26)dimethyltransferance in which 246arginine is important for the enzyme activity. Gene 226 (1999) 73–81. [PMID: 10048958]
[EC 2.1.1.216 created 2011 (EC 2.1.1.32 created 1972, part transferred 2011 to EC 2.1.1.216)]
 
 
EC 2.1.1.217     
Accepted name: tRNA (adenine22-N1)-methyltransferase
Reaction: S-adenosyl-L-methionine + adenine22 in tRNA = S-adenosyl-L-homocysteine + N1-methyladenine22 in tRNA
Other name(s): TrmK; YqfN; Sp1610 (gene name); tRNA: m1A22 methyltransferase
Systematic name: S-adenosyl-L-methionine:tRNA (adenine22-N1)-methyltransferase
Comments: The enzyme specifically methylates adenine22 in tRNA.
References:
1.  Ta, H.M. and Kim, K.K. Crystal structure of Streptococcus pneumoniae Sp1610, a putative tRNA methyltransferase, in complex with S-adenosyl-L-methionine. Protein Sci. 19 (2010) 617–624. [PMID: 20052680]
2.  Roovers, M., Kaminska, K.H., Tkaczuk, K.L., Gigot, D., Droogmans, L. and Bujnicki, J.M. The YqfN protein of Bacillus subtilis is the tRNA: m1A22 methyltransferase (TrmK). Nucleic Acids Res. 36 (2008) 3252–3262. [PMID: 18420655]
[EC 2.1.1.217 created 2011 (EC 2.1.1.36 created 1972, part transferred 2011 to EC 2.1.1.217)]
 
 
EC 2.1.1.218     
Accepted name: tRNA (adenine9-N1)-methyltransferase
Reaction: S-adenosyl-L-methionine + adenine9 in tRNA = S-adenosyl-L-homocysteine + N1-methyladenine9 in tRNA
Other name(s): Trm10p (ambiguous); tRNA(m1G9/m1A9)-methyltransferase; tRNA(m1G9/m1A9)MTase; TK0422p (gene name); tRNA m1A9-methyltransferase; tRNA m1A9 Mtase
Systematic name: S-adenosyl-L-methionine:tRNA (adenine9-N1)-methyltransferase
Comments: The enzyme from Sulfolobus acidocaldarius specifically methylates adenine9 in tRNA [1]. The bifunctional enzyme from Thermococcus kodakaraensis also catalyses the methylation of guanine9 in tRNA (cf. EC 2.1.1.221, tRNA (guanine9-N1)-methyltransferase).
References:
1.  Kempenaers, M., Roovers, M., Oudjama, Y., Tkaczuk, K.L., Bujnicki, J.M. and Droogmans, L. New archaeal methyltransferases forming 1-methyladenosine or 1-methyladenosine and 1-methylguanosine at position 9 of tRNA. Nucleic Acids Res. 38 (2010) 6533–6543. [PMID: 20525789]
[EC 2.1.1.218 created 2011 (EC 2.1.1.36 created 1972, part transferred 2011 to EC 2.1.1.218)]
 
 
EC 2.1.1.219     
Accepted name: tRNA (adenine57-N1/adenine58-N1)-methyltransferase
Reaction: 2 S-adenosyl-L-methionine + adenine57/adenine58 in tRNA = 2 S-adenosyl-L-homocysteine + N1-methyladenine57/N1-methyladenine58 in tRNA
Other name(s): TrmI; PabTrmI; AqTrmI; MtTrmI
Systematic name: S-adenosyl-L-methionine:tRNA (adenine57/adenine58-N1)-methyltransferase
Comments: The enzyme catalyses the formation of N1-methyladenine at two adjacent positions (57 and 58) in the T-loop of certain tRNAs (e.g. tRNAAsp). Methyladenosine at position 57 is an obligatory intermediate for the synthesis of methylinosine, which is commonly found at position 57 of archaeal tRNAs.
References:
1.  Roovers, M., Wouters, J., Bujnicki, J.M., Tricot, C., Stalon, V., Grosjean, H. and Droogmans, L. A primordial RNA modification enzyme: the case of tRNA (m1A) methyltransferase. Nucleic Acids Res. 32 (2004) 465–476. [PMID: 14739239]
2.  Guelorget, A., Roovers, M., Guerineau, V., Barbey, C., Li, X. and Golinelli-Pimpaneau, B. Insights into the hyperthermostability and unusual region-specificity of archaeal Pyrococcus abyssi tRNA m1A57/58 methyltransferase. Nucleic Acids Res. 38 (2010) 6206–6218. [PMID: 20483913]
[EC 2.1.1.219 created 2011 (EC 2.1.1.36 created 1972, part transferred 2011 to EC 2.1.1.219)]
 
 
EC 2.1.1.220     
Accepted name: tRNA (adenine58-N1)-methyltransferase
Reaction: S-adenosyl-L-methionine + adenine58 in tRNA = S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNA
Other name(s): tRNA m1A58 methyltransferase; tRNA (m1A58) methyltransferase; TrmI; tRNA (m1A58) Mtase; Rv2118cp; Gcd10p-Gcd14p; Trm61p-Trm6p
Systematic name: S-adenosyl-L-methionine:tRNA (adenine58-N1)-methyltransferase
Comments: The enzyme specifically methylates adenine58 in tRNA. The methylation of A58 is critical for maintaining the stability of initiator tRNAMet in yeast [3].
References:
1.  Droogmans, L., Roovers, M., Bujnicki, J.M., Tricot, C., Hartsch, T., Stalon, V. and Grosjean, H. Cloning and characterization of tRNA (m1A58) methyltransferase (TrmI) from Thermus thermophilus HB27, a protein required for cell growth at extreme temperatures. Nucleic Acids Res. 31 (2003) 2148–2156. [PMID: 12682365]
2.  Varshney, U., Ramesh, V., Madabushi, A., Gaur, R., Subramanya, H.S. and RajBhandary, U.L. Mycobacterium tuberculosis Rv2118c codes for a single-component homotetrameric m1A58 tRNA methyltransferase. Nucleic Acids Res. 32 (2004) 1018–1027. [PMID: 14960715]
3.  Anderson, J., Phan, L. and Hinnebusch, A.G. The Gcd10p/Gcd14p complex is the essential two-subunit tRNA(1-methyladenosine) methyltransferase of Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 97 (2000) 5173–5178. [PMID: 10779558]
[EC 2.1.1.220 created 2011 (EC 2.1.1.36 created 1972, part transferred 2011 to EC 2.1.1.220)]
 
 
EC 2.1.1.221     
Accepted name: tRNA (guanine9-N1)-methyltransferase
Reaction: S-adenosyl-L-methionine + guanine9 in tRNA = S-adenosyl-L-homocysteine + N1-methylguanine9 in tRNA
Other name(s): Trm10p (ambiguous); tRNA(m1G9/m1A9)-methyltransferase; tRNA(m1G9/m1A9)MTase; tRNA (guanine-N(1)-)-methyltransferase; tRNA m1G9-methyltransferase; tRNA m1G9 MTase
Systematic name: S-adenosyl-L-methionine:tRNA (guanine9-N1)-methyltransferase
Comments: The enzyme from Saccharomyces cerevisiae specifically methylates guanine9 [1,2]. The bifunctional enzyme from Thermococcus kodakaraensis also catalyses the methylation of adenine9 in tRNA (cf. EC 2.1.1.218, tRNA (adenine9-N1)-methyltransferase) [1].
References:
1.  Kempenaers, M., Roovers, M., Oudjama, Y., Tkaczuk, K.L., Bujnicki, J.M. and Droogmans, L. New archaeal methyltransferases forming 1-methyladenosine or 1-methyladenosine and 1-methylguanosine at position 9 of tRNA. Nucleic Acids Res. 38 (2010) 6533–6543. [PMID: 20525789]
2.  Jackman, J.E., Montange, R.K., Malik, H.S. and Phizicky, E.M. Identification of the yeast gene encoding the tRNA m1G methyltransferase responsible for modification at position 9. RNA 9 (2003) 574–585. [PMID: 12702816]
[EC 2.1.1.221 created 2011 (EC 2.1.1.31 created 1971, part transferred 2011 to EC 2.1.1.221)]
 
 
EC 2.1.1.222     
Accepted name: 2-polyprenyl-6-hydroxyphenol methylase
Reaction: S-adenosyl-L-methionine + 3-(all-trans-polyprenyl)benzene-1,2-diol = S-adenosyl-L-homocysteine + 2-methoxy-6-(all-trans-polyprenyl)phenol
Other name(s): ubiG (gene name, ambiguous); ubiG methyltransferase (ambiguous); 2-octaprenyl-6-hydroxyphenol methylase
Systematic name: S-adenosyl-L-methionine:3-(all-trans-polyprenyl)benzene-1,2-diol 2-O-methyltransferase
Comments: UbiG catalyses both methylation steps in ubiquinone biosynthesis in Escherichia coli. The second methylation is classified as EC 2.1.1.64 (3-demethylubiquinol 3-O-methyltransferase) [2]. In eukaryotes Coq3 catalyses the two methylation steps in ubiquinone biosynthesis. However, while the second methylation is common to both enzymes, the first methylation by Coq3 occurs at a different position within the pathway, and thus involves a different substrate and is classified as EC 2.1.1.114 (polyprenyldihydroxybenzoate methyltransferase). The substrate of the eukaryotic enzyme (3,4-dihydroxy-5-all-trans-polyprenylbenzoate) differs by an additional carboxylate moiety.
References:
1.  Poon, W.W., Barkovich, R.J., Hsu, A.Y., Frankel, A., Lee, P.T., Shepherd, J.N., Myles, D.C. and Clarke, C.F. Yeast and rat Coq3 and Escherichia coli UbiG polypeptides catalyze both O-methyltransferase steps in coenzyme Q biosynthesis. J. Biol. Chem. 274 (1999) 21665–21672. [PMID: 10419476]
2.  Hsu, A.Y., Poon, W.W., Shepherd, J.A., Myles, D.C. and Clarke, C.F. Complementation of coq3 mutant yeast by mitochondrial targeting of the Escherichia coli UbiG polypeptide: evidence that UbiG catalyzes both O-methylation steps in ubiquinone biosynthesis. Biochemistry 35 (1996) 9797–9806. [PMID: 8703953]
[EC 2.1.1.222 created 2011, modified 2013]
 
 
EC 2.1.1.223     
Accepted name: tRNA1Val (adenine37-N6)-methyltransferase
Reaction: S-adenosyl-L-methionine + adenine37 in tRNA1Val = S-adenosyl-L-homocysteine + N6-methyladenine37 in tRNA1Val
Other name(s): YfiC
Systematic name: S-adenosyl-L-methionine:tRNA1Val (adenine37-N6)-methyltransferase
Comments: The enzyme specifically methylates adenine37 in tRNA1Val (anticodon cmo5UAC).
References:
1.  Golovina, A.Y., Sergiev, P.V., Golovin, A.V., Serebryakova, M.V., Demina, I., Govorun, V.M. and Dontsova, O.A. The yfiC gene of E. coli encodes an adenine-N6 methyltransferase that specifically modifies A37 of tRNA1Val(cmo5UAC). RNA 15 (2009) 1134–1141. [PMID: 19383770]
[EC 2.1.1.223 created 2011]
 
 
EC 2.1.1.224     
Accepted name: 23S rRNA (adenine2503-C8)-methyltransferase
Reaction: 2 S-adenosyl-L-methionine + adenine2503 in 23S rRNA + 2 reduced [2Fe-2S] ferredoxin = S-adenosyl-L-homocysteine + L-methionine + 5′-deoxyadenosine + 8-methyladenine2503 in 23S rRNA + 2 oxidized [2Fe-2S] ferredoxin
Other name(s): Cfr (gene name)
Systematic name: S-adenosyl-L-methionine:23S rRNA (adenine2503-C8)-methyltransferase
Comments: This enzyme is a member of the ’AdoMet radical’ (radical SAM) family. S-Adenosyl-L-methionine acts as both a radical generator and as the source of the appended methyl group. It contains an [4Fe-4S] cluster [3,6,7]. Cfr is an plasmid-acquired methyltransferase that protects cells from the action of antibiotics [1]. The enzyme methylates adenosine at position 2503 of 23S rRNA by a radical mechanism, transferring a CH2 group from S-adenosyl-L-methionine while retaining the hydrogen at the C-8 position of the adenine. Cfr first transfers an CH2 group to a conserved cysteine (Cys338 in Staphylococcus aureus) [7], the generated radical from a second S-adenosyl-L-methionine then attacks the methyl group, exctracting a hydrogen. The formed radical forms a covalent intermediate with the adenine group of the tRNA [8]. The enzyme will also methylate 2-methyladenine produced by the action of EC 2.1.1.192 [23S rRNA (adenine2503-C2)-methyltransferase].
References:
1.  Giessing, A.M., Jensen, S.S., Rasmussen, A., Hansen, L.H., Gondela, A., Long, K., Vester, B. and Kirpekar, F. Identification of 8-methyladenosine as the modification catalyzed by the radical SAM methyltransferase Cfr that confers antibiotic resistance in bacteria. RNA 15 (2009) 327–336. [PMID: 19144912]
2.  Kaminska, K.H., Purta, E., Hansen, L.H., Bujnicki, J.M., Vester, B. and Long, K.S. Insights into the structure, function and evolution of the radical-SAM 23S rRNA methyltransferase Cfr that confers antibiotic resistance in bacteria. Nucleic Acids Res. 38 (2010) 1652–1663. [PMID: 20007606]
3.  Yan, F., LaMarre, J.M., Röhrich, R., Wiesner, J., Jomaa, H., Mankin, A.S. and Fujimori, D.G. RlmN and Cfr are radical SAM enzymes involved in methylation of ribosomal RNA. J. Am. Chem. Soc. 132 (2010) 3953–3964. [PMID: 20184321]
4.  Yan, F. and Fujimori, D.G. RNA methylation by radical SAM enzymes RlmN and Cfr proceeds via methylene transfer and hydride shift. Proc. Natl. Acad. Sci. USA 108 (2011) 3930–3934. [PMID: 21368151]
5.  Grove, T.L., Benner, J.S., Radle, M.I., Ahlum, J.H., Landgraf, B.J., Krebs, C. and Booker, S.J. A radically different mechanism for S-adenosylmethionine-dependent methyltransferases. Science 332 (2011) 604–607. [PMID: 21415317]
6.  Boal, A.K., Grove, T.L., McLaughlin, M.I., Yennawar, N.H., Booker, S.J. and Rosenzweig, A.C. Structural basis for methyl transfer by a radical SAM enzyme. Science 332 (2011) 1089–1092. [PMID: 21527678]
7.  Grove, T.L., Radle, M.I., Krebs, C. and Booker, S.J. Cfr and RlmN contain a single [4Fe-4S] cluster, which directs two distinct reactivities for S-adenosylmethionine: methyl transfer by SN2 displacement and radical generation. J. Am. Chem. Soc. 133 (2011) 19586–19589. [PMID: 21916495]
8.  Grove, T.L., Livada, J., Schwalm, E.L., Green, M.T., Booker, S.J. and Silakov, A. A substrate radical intermediate in catalysis by the antibiotic resistance protein Cfr. Nat. Chem. Biol. 9 (2013) 422–427. [PMID: 23644479]
[EC 2.1.1.224 created 2011, modified 2014]
 
 
EC 2.1.1.225     
Accepted name: tRNA:m4X modification enzyme
Reaction: (1) S-adenosyl-L-methionine + cytidine4 in tRNAPro = S-adenosyl-L-homocysteine + 2′-O-methylcytidine4 in tRNAPro
(2) S-adenosyl-L-methionine + cytidine4 in tRNAGly(GCC) = S-adenosyl-L-homocysteine + 2′-O-methylcytidine4 in tRNAGly(GCC)
(3) S-adenosyl-L-methionine + adenosine4 in tRNAHis = S-adenosyl-L-homocysteine + 2′-O-methyladenosine4 in tRNAHis
Other name(s): TRM13; Trm13p; tRNA:Xm4 modification enzyme
Systematic name: S-adenosyl-L-methionine:tRNAPro/His/Gly(GCC) (cytidine/adenosine4-2′-O)-methyltransferase
Comments: The enzyme from Saccharomyces cerevisiae 2′-O-methylates cytidine4 in tRNAPro and tRNAGly(GCC), and adenosine4 in tRNAHis.
References:
1.  Wilkinson, M.L., Crary, S.M., Jackman, J.E., Grayhack, E.J. and Phizicky, E.M. The 2′-O-methyltransferase responsible for modification of yeast tRNA at position 4. RNA 13 (2007) 404–413. [PMID: 17242307]
[EC 2.1.1.225 created 2011]
 
 
EC 2.1.1.226     
Accepted name: 23S rRNA (cytidine1920-2′-O)-methyltransferase
Reaction: S-adenosyl-L-methionine + cytidine1920 in 23S rRNA = S-adenosyl-L-homocysteine + 2′-O-methylcytidine1920 in 23S rRNA
Other name(s): TlyA (ambiguous)
Systematic name: S-adenosyl-L-methionine:23S rRNA (cytidine1920-2′-O)-methyltransferase
Comments: The bifunctional enzyme from Mycobacterium tuberculosis 2′-O-methylates cytidine1920 in helix 69 of 23S rRNA and cytidine1409 in helix 44 of 16S rRNA (cf. EC 2.1.1.227, 16S rRNA (cytidine1409-2′-O)-methyltransferase). These methylations result in increased susceptibility to the antibiotics capreomycin and viomycin.
References:
1.  Johansen, S.K., Maus, C.E., Plikaytis, B.B. and Douthwaite, S. Capreomycin binds across the ribosomal subunit interface using tlyA-encoded 2′-O-methylations in 16S and 23S rRNAs. Mol. Cell 23 (2006) 173–182. [PMID: 16857584]
2.  Maus, C.E., Plikaytis, B.B. and Shinnick, T.M. Mutation of tlyA confers capreomycin resistance in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 49 (2005) 571–577. [PMID: 15673735]
[EC 2.1.1.226 created 2011]
 
 
EC 2.1.1.227     
Accepted name: 16S rRNA (cytidine1409-2′-O)-methyltransferase
Reaction: S-adenosyl-L-methionine + cytidine1409 in 16S rRNA = S-adenosyl-L-homocysteine + 2′-O-methylcytidine1409 in 16S rRNA
Other name(s): TlyA (ambiguous)
Systematic name: S-adenosyl-L-methionine:16S rRNA (cytidine1409-2′-O)-methyltransferase
Comments: The bifunctional enzyme from Mycobacterium tuberculosis 2′-O-methylates cytidine1409 in helix 44 of 16S rRNA and cytidine1920 in helix 69 of 23S rRNA (cf. EC 2.1.1.226, 23S rRNA (cytidine1920-2′-O)-methyltransferase).
References:
1.  Johansen, S.K., Maus, C.E., Plikaytis, B.B. and Douthwaite, S. Capreomycin binds across the ribosomal subunit interface using tlyA-encoded 2′-O-methylations in 16S and 23S rRNAs. Mol. Cell 23 (2006) 173–182. [PMID: 16857584]
2.  Maus, C.E., Plikaytis, B.B. and Shinnick, T.M. Mutation of tlyA confers capreomycin resistance in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 49 (2005) 571–577. [PMID: 15673735]
[EC 2.1.1.227 created 2011]
 
 
EC 2.1.1.228     
Accepted name: tRNA (guanine37-N1)-methyltransferase
Reaction: S-adenosyl-L-methionine + guanine37 in tRNA = S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA
Other name(s): TrmD; tRNA (m1G37) methyltransferase; transfer RNA (m1G37) methyltransferase; Trm5p; TRMT5; tRNA-(N1G37) methyltransferase; MJ0883 (gene name)
Systematic name: S-adenosyl-L-methionine:tRNA (guanine37-N1)-methyltransferase
Comments: This enzyme is important for the maintenance of the correct reading frame during translation. Unlike TrmD from Escherichia coli, which recognizes the G36pG37 motif preferentially, the human enzyme (encoded by TRMT5) also methylates inosine at position 37 [4].
References:
1.  Takeda, H., Toyooka, T., Ikeuchi, Y., Yokobori, S., Okadome, K., Takano, F., Oshima, T., Suzuki, T., Endo, Y. and Hori, H. The substrate specificity of tRNA (m1G37) methyltransferase (TrmD) from Aquifex aeolicus. Genes Cells 11 (2006) 1353–1365. [PMID: 17121543]
2.  Lee, C., Kramer, G., Graham, D.E. and Appling, D.R. Yeast mitochondrial initiator tRNA is methylated at guanosine 37 by the Trm5-encoded tRNA (guanine-N1-)-methyltransferase. J. Biol. Chem. 282 (2007) 27744–27753. [PMID: 17652090]
3.  O'Dwyer, K., Watts, J.M., Biswas, S., Ambrad, J., Barber, M., Brule, H., Petit, C., Holmes, D.J., Zalacain, M. and Holmes, W.M. Characterization of Streptococcus pneumoniae TrmD, a tRNA methyltransferase essential for growth. J. Bacteriol. 186 (2004) 2346–2354. [PMID: 15060037]
4.  Brule, H., Elliott, M., Redlak, M., Zehner, Z.E. and Holmes, W.M. Isolation and characterization of the human tRNA-(N1G37) methyltransferase (TRM5) and comparison to the Escherichia coli TrmD protein. Biochemistry 43 (2004) 9243–9255. [PMID: 15248782]
5.  Goto-Ito, S., Ito, T., Ishii, R., Muto, Y., Bessho, Y. and Yokoyama, S. Crystal structure of archaeal RNA(m1G37)methyltransferase aTrm5. Proteins 72 (2008) 1274–1289. [PMID: 18384044]
6.  Ahn, H.J., Kim, H.W., Yoon, H.J., Lee, B.I., Suh, S.W. and Yang, J.K. Crystal structure of tRNA(m1G37)methyltransferase: insights into tRNA recognition. EMBO J. 22 (2003) 2593–2603. [PMID: 12773376]
[EC 2.1.1.228 created 2011 (EC 2.1.1.31 created 1971, part transferred 2011 to EC 2.1.1.228)]
 
 
EC 2.1.1.229     
Accepted name: tRNA (carboxymethyluridine34-5-O)-methyltransferase
Reaction: S-adenosyl-L-methionine + carboxymethyluridine34 in tRNA = S-adenosyl-L-homocysteine + 5-(2-methoxy-2-oxoethyl)uridine34 in tRNA
Glossary: 5-methoxycarboxymethyluridine = 5-(2-methoxy-2-oxoethyl)uridine
Other name(s): ALKBH8; ABH8; Trm9; tRNA methyltransferase 9
Systematic name: S-adenosyl-L-methionine:tRNA (carboxymethyluridine34-5-O)-methyltransferase
Comments: The enzyme catalyses the posttranslational modification of uridine residues at the wobble position 34 of the anticodon loop of tRNA.
References:
1.  Fu, D., Brophy, J.A., Chan, C.T., Atmore, K.A., Begley, U., Paules, R.S., Dedon, P.C., Begley, T.J. and Samson, L.D. Human AlkB homolog ABH8 Is a tRNA methyltransferase required for wobble uridine modification and DNA damage survival. Mol. Cell Biol. 30 (2010) 2449–2459. [PMID: 20308323]
2.  Songe-Møller, L., van den Born, E., Leihne, V., Vågbø, C.B., Kristoffersen, T., Krokan, H.E., Kirpekar, F., Falnes, P.Ø. and Klungland, A. Mammalian ALKBH8 possesses tRNA methyltransferase activity required for the biogenesis of multiple wobble uridine modifications implicated in translational decoding. Mol. Cell Biol. 30 (2010) 1814–1827. [PMID: 20123966]
3.  Kalhor, H.R. and Clarke, S. Novel methyltransferase for modified uridine residues at the wobble position of tRNA. Mol. Cell Biol. 23 (2003) 9283–9292. [PMID: 14645538]
[EC 2.1.1.229 created 2011]
 
 
EC 2.1.1.230     
Accepted name: 23S rRNA (adenosine1067-2′-O)-methyltransferase
Reaction: S-adenosyl-L-methionine + adenosine1067 in 23S rRNA = S-adenosyl-L-homocysteine + 2′-O-methyladenosine1067 in 23S rRNA
Other name(s): 23S rRNA A1067 2′-methyltransferase; thiostrepton-resistance methylase; nosiheptide-resistance methyltransferase
Systematic name: S-adenosyl-L-methionine:23S rRNA (adenosine1067-2′-O)-methyltransferase
Comments: The methylase that is responsible for autoimmunity in the thiostrepton producer Streptomyces azureus, renders ribosomes completely resistant to thiostrepton [2].
References:
1.  Bechthold, A. and Floss, H.G. Overexpression of the thiostrepton-resistance gene from Streptomyces azureus in Escherichia coli and characterization of recognition sites of the 23S rRNA A1067 2′-methyltransferase in the guanosine triphosphatase center of 23S ribosomal RNA. Eur. J. Biochem. 224 (1994) 431–437. [PMID: 7925357]
2.  Thompson, J., Schmidt, F. and Cundliffe, E. Site of action of a ribosomal RNA methylase conferring resistance to thiostrepton. J. Biol. Chem. 257 (1982) 7915–7917. [PMID: 6806287]
3.  Thompson, J. and Cundliffe, E. Purification and properties of an RNA methylase produced by Streptomyces azureus and involved in resistance to thiostrepton. J. Gen. Microbiol. 124 (1981) 291–297.
4.  Yang, H., Wang, Z., Shen, Y., Wang, P., Jia, X., Zhao, L., Zhou, P., Gong, R., Li, Z., Yang, Y., Chen, D., Murchie, A.I. and Xu, Y. Crystal structure of the nosiheptide-resistance methyltransferase of Streptomyces actuosus. Biochemistry 49 (2010) 6440–6450. [PMID: 20550164]
[EC 2.1.1.230 created 2011]
 
 
EC 2.1.1.231     
Accepted name: flavonoid 4′-O-methyltransferase
Reaction: S-adenosyl-L-methionine + a 4′-hydroxyflavanone = S-adenosyl-L-homocysteine + a 4′-methoxyflavanone
Glossary: naringenin = 4′,5,7-trihydroxyflavan-4-one
Other name(s): SOMT-2; 4′-hydroxyisoflavone methyltransferase
Systematic name: S-adenosyl-L-methionine:flavonoid 4′-O-methyltransferase
Comments: The enzyme catalyses the 4′-methylation of naringenin. In vitro it catalyses the 4′-methylation of apigenin, quercetin, daidzein and genistein.
References:
1.  Kim, D.H., Kim, B.G., Lee, Y., Ryu, J.Y., Lim, Y., Hur, H.G. and Ahn, J.H. Regiospecific methylation of naringenin to ponciretin by soybean O-methyltransferase expressed in Escherichia coli. J. Biotechnol. 119 (2005) 155–162. [PMID: 15961179]
[EC 2.1.1.231 created 2011]
 
 
EC 2.1.1.232     
Accepted name: naringenin 7-O-methyltransferase
Reaction: S-adenosyl-L-methionine + (2S)-naringenin = S-adenosyl-L-homocysteine + (2S)-sakuranetin
Glossary: (2S)-naringenin = (2S)-5,7,4′-trihydroxyflavan-4-one
(2S)-sakuranetin = (2S)-5,4′-dihydroxy-7-methoxyflavan-4-one
Other name(s): NOMT
Systematic name: S-adenosyl-L-methionine:(2S)-5,7,4′-trihydroxyflavanone 7-O-methyltransferase
Comments: The enzyme is involved in the biosynthesis of the sakuranetin, an inducible defense mechanism of the plant Oryza sativa (Asian rice) against pathogen attack.
References:
1.  Rakwal, R., Agrawal, G.K., Yonekura, M. and Kodama, O. Naringenin 7-O-methyltransferase involved in the biosynthesis of the flavanone phytoalexin sakuranetin from rice (Oryza sativa L.). Plant Sci. 155 (2000) 213–221. [PMID: 10814825]
[EC 2.1.1.232 created 2011]
 
 
EC 2.1.1.233     
Accepted name: [phosphatase 2A protein]-leucine-carboxy methyltransferase
Reaction: S-adenosyl-L-methionine + [phosphatase 2A protein]-leucine = S-adenosyl-L-homocysteine + [phosphatase 2A protein]-leucine methyl ester
Other name(s): leucine carboxy methyltransferase-1; LCMT1
Systematic name: S-adenosyl-L-methionine:[phosphatase 2A protein]-leucine O-methyltransferase
Comments: Methylates the C-terminal leucine of phosphatase 2A. A key regulator of protein phosphatase 2A. The methyl ester is hydrolysed by EC 3.1.1.89 (protein phosphatase methylesterase-1). Occurs mainly in the cytoplasm, Golgi region and late endosomes.
References:
1.  De Baere, I., Derua, R., Janssens, V., Van Hoof, C., Waelkens, E., Merlevede, W. and Goris, J. Purification of porcine brain protein phosphatase 2A leucine carboxyl methyltransferase and cloning of the human homologue. Biochemistry 38 (1999) 16539–16547. [PMID: 10600115]
2.  Tsai, M.L., Cronin, N. and Djordjevic, S. The structure of human leucine carboxyl methyltransferase 1 that regulates protein phosphatase PP2A. Acta Crystallogr. D Biol. Crystallogr. 67 (2011) 14–24. [PMID: 21206058]
[EC 2.1.1.233 created 2011]
 
 
EC 2.1.1.234     
Accepted name: dTDP-3-amino-3,4,6-trideoxy-α-D-glucopyranose N,N-dimethyltransferase
Reaction: 2 S-adenosyl-L-methionine + dTDP-3-amino-3,4,6-trideoxy-α-D-glucopyranose = 2 S-adenosyl-L-homocysteine + dTDP-3-dimethylamino-3,4,6-trideoxy-α-D-glucopyranose
Glossary: α-D-desosamine = 3-dimethylamino-3,4,6-trideoxy-α-D-glucopyranose
dTDP-3-dimethylamino-3,4,6-trideoxy-α-D-glucopyranose = dTDP-D-desosamine
Other name(s): DesVI
Systematic name: S-adenosyl-L-methionine:dTDP-3-amino-3,4,6-trideoxy-α-D-glucopyranose 3-N,N-dimethyltransferase
Comments: The enzyme is involved in the biosynthesis of desosamine, a 3-(dimethylamino)-3,4,6-trideoxyhexose found in certain macrolide antibiotics such as erthyromycin, azithromycin, and clarithromycin.
References:
1.  Chen, H., Yamase, H., Murakami, K., Chang, C.W., Zhao, L., Zhao, Z. and Liu, H.W. Expression, purification, and characterization of two N,N-dimethyltransferases, tylM1 and desVI, involved in the biosynthesis of mycaminose and desosamine. Biochemistry 41 (2002) 9165–9183. [PMID: 12119032]
2.  Burgie, E.S. and Holden, H.M. Three-dimensional structure of DesVI from Streptomyces venezuelae: a sugar N,N-dimethyltransferase required for dTDP-desosamine biosynthesis. Biochemistry 47 (2008) 3982–3988. [PMID: 18327916]
[EC 2.1.1.234 created 2011]
 
 
EC 2.1.1.235     
Accepted name: dTDP-3-amino-3,6-dideoxy-α-D-glucopyranose N,N-dimethyltransferase
Reaction: 2 S-adenosyl-L-methionine + dTDP-3-amino-3,6-dideoxy-α-D-glucopyranose = 2 S-adenosyl-L-homocysteine + dTDP-3-dimethylamino-3,6-dideoxy-α-D-glucopyranose
Glossary: dTDP-D-mycaminose = dTDP-3-dimethylamino-3,6-dideoxy-α-D-glucopyranose
Other name(s): TylM1
Systematic name: S-adenosyl-L-methionine:dTDP-3-amino-3,6-dideoxy-α-D-glucopyranose 3-N,N-dimethyltransferase
Comments: The enzyme is involved in the biosynthesis of mycaminose, an essential structural component of the macrolide antibiotic tylosin, which is produced by the bacterium Streptomyces fradiae.
References:
1.  Chen, H., Yamase, H., Murakami, K., Chang, C.W., Zhao, L., Zhao, Z. and Liu, H.W. Expression, purification, and characterization of two N,N-dimethyltransferases, tylM1 and desVI, involved in the biosynthesis of mycaminose and desosamine. Biochemistry 41 (2002) 9165–9183. [PMID: 12119032]
2.  Carney, A.E. and Holden, H.M. Molecular architecture of TylM1 from Streptomyces fradiae: an N,N-dimethyltransferase involved in the production of dTDP-D-mycaminose. Biochemistry 50 (2011) 780–787. [PMID: 21142177]
[EC 2.1.1.235 created 2011]
 
 
EC 2.1.1.236     
Accepted name: dTDP-3-amino-3,6-dideoxy-α-D-galactopyranose N,N-dimethyltransferase
Reaction: 2 S-adenosyl-L-methionine + dTDP-3-amino-3,6-dideoxy-α-D-galactopyranose = 2 S-adenosyl-L-homocysteine + dTDP-3-dimethylamino-3,6-dideoxy-α-D-galactopyranose
Glossary: dTDP-3-dimethylamino-3,6-dideoxy-α-D-galactopyranose = dTDP-D-ravidosamine
Other name(s): RavNMT
Systematic name: S-adenosyl-L-methionine:dTDP-3-amino-3,6-dideoxy-α-D-galactopyranose 3-N,N-dimethyltransferase
Comments: The enzyme is involved in the synthesis of dTDP-D-ravidosamine, the amino sugar moiety of the antibiotic ravidomycin V, which is produced by the bacterium Streptomyces ravidus.
References:
1.  Kharel, M.K., Lian, H. and Rohr, J. Characterization of the TDP-D-ravidosamine biosynthetic pathway: one-pot enzymatic synthesis of TDP-D-ravidosamine from thymidine-5-phosphate and glucose-1-phosphate. Org. Biomol. Chem. 9 (2011) 1799–1808. [PMID: 21264378]
[EC 2.1.1.236 created 2011]
 
 
EC 2.1.1.237     
Accepted name: mycinamicin III 3′′-O-methyltransferase
Reaction: S-adenosyl-L-methionine + mycinamicin III = S-adenosyl-L-homocysteine + mycinamicin IV
Glossary: mycinamicin III = [(2R,3R,4E,6E,9R,11S,12S,13S,14E)-2-ethyl-9,11,13-trimethyl-8,16-dioxo-12-{[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy}oxacyclohexadeca-4,6,14-trien-3-yl]methyl 6-deoxy-2-O-methyl-β-D-allopyranoside
mycinamicin IV = [(2R,3R,4E,6E,9R,11S,12S,13S,14E)-2-ethyl-9,11,13-trimethyl-8,16-dioxo-12-{[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy}oxacyclohexadeca-4,6,14-trien-3-yl]methyl 6-deoxy-2,3-di-O-methyl-β-D-allopyranoside
Other name(s): MycF
Systematic name: S-adenosyl-L-methionine:mycinamicin III 3′′-O-methyltransferase
Comments: The enzyme is involved in the biosynthesis of mycinamicin macrolide antibiotics.
References:
1.  Li, S., Anzai, Y., Kinoshita, K., Kato, F. and Sherman, D.H. Functional analysis of MycE and MycF, two O-methyltransferases involved in the biosynthesis of mycinamicin macrolide antibiotics. ChemBioChem 10 (2009) 1297–1301. [PMID: 19415708]
[EC 2.1.1.237 created 2011]
 
 
EC 2.1.1.238     
Accepted name: mycinamicin VI 2′′-O-methyltransferase
Reaction: S-adenosyl-L-methionine + mycinamicin VI = S-adenosyl-L-homocysteine + mycinamicin III
Glossary: mycinamicin III = [(2R,3R,4E,6E,9R,11S,12S,13S,14E)-2-ethyl-9,11,13-trimethyl-8,16-dioxo-12-{[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy}oxacyclohexadeca-4,6,14-trien-3-yl]methyl 6-deoxy-2-O-methyl-β-D-allopyranoside
mycinamicin VI = [(2R,3R,4E,6E,9R,11S,12S,13S,14E)-2-ethyl-9,11,13-trimethyl-8,16-dioxo-12-{[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy}oxacyclohexadeca-4,6,14-trien-3-yl]methyl 6-deoxy-β-D-allopyranoside
Other name(s): MycE
Systematic name: S-adenosyl-L-methionine:mycinamicin VI 2′′-O-methyltransferase
Comments: The enzyme is involved in the biosynthesis of mycinamicin macrolide antibiotics. Requires Mg2+ for optimal activity.
References:
1.  Li, S., Anzai, Y., Kinoshita, K., Kato, F. and Sherman, D.H. Functional analysis of MycE and MycF, two O-methyltransferases involved in the biosynthesis of mycinamicin macrolide antibiotics. ChemBioChem 10 (2009) 1297–1301. [PMID: 19415708]
[EC 2.1.1.238 created 2011]
 
 
EC 2.1.1.239     
Accepted name: L-olivosyl-oleandolide 3-O-methyltransferase
Reaction: S-adenosyl-L-methionine + L-olivosyl-oleandolide = S-adenosyl-L-homocysteine + L-oleandrosyl-oleandolide
Other name(s): OleY
Systematic name: S-adenosyl-L-methionine:L-olivosyl-oleandolide B 3-O-methyltransferase
Comments: The enzyme is involved in the biosynthesis of the macrolide antibiotic oleandomycin in Streptomyces antibioticus. It can also act on other monoglycosylated macrolactones, including L-rhamnosyl-erythronolide B and L-mycarosyl-erythronolide B.
References:
1.  Rodriguez, L., Rodriguez, D., Olano, C., Brana, A.F., Mendez, C. and Salas, J.A. Functional analysis of OleY L-oleandrosyl 3-O-methyltransferase of the oleandomycin biosynthetic pathway in Streptomyces antibioticus. J. Bacteriol. 183 (2001) 5358–5363. [PMID: 11514520]
[EC 2.1.1.239 created 2012]
 
 
EC 2.1.1.240     
Accepted name: trans-resveratrol di-O-methyltransferase
Reaction: 2 S-adenosyl-L-methionine + trans-resveratrol = 2 S-adenosyl-L-homocysteine + pterostilbene (overall reaction)
(1a) S-adenosyl-L-methionine + trans-resveratrol = S-adenosyl-L-homocysteine + 3-methoxy-4′,5-dihydroxy-trans-stilbene
(1b) S-adenosyl-L-methionine + 3-methoxy-4′,5-dihydroxy-trans-stilbene = S-adenosyl-L-homocysteine + pterostilbene
Glossary: 3-methoxy-4′,5-dihydroxy-trans-stilbene = resveratrol monomethyl ether
pterostilbene = 3,5-dimethoxy-4′-hydroxy-trans-stilbene
trans-resveratrol = 3,4′,5-trihydroxy-trans-stilbene
Other name(s): ROMT; resveratrol O-methyltransferase; pterostilbene synthase
Systematic name: S-adenosyl-L-methionine:trans-resveratrol 3,5-O-dimethyltransferase
Comments: The enzyme catalyses the biosynthesis of pterostilbene from resveratrol.
References:
1.  Schmidlin, L., Poutaraud, A., Claudel, P., Mestre, P., Prado, E., Santos-Rosa, M., Wiedemann-Merdinoglu, S., Karst, F., Merdinoglu, D. and Hugueney, P. A stress-inducible resveratrol O-methyltransferase involved in the biosynthesis of pterostilbene in grapevine. Plant Physiol. 148 (2008) 1630–1639. [PMID: 18799660]
[EC 2.1.1.240 created 2012]
 
 
EC 2.1.1.241     
Accepted name: 2,4,7-trihydroxy-1,4-benzoxazin-3-one-glucoside 7-O-methyltransferase
Reaction: S-adenosyl-L-methionine + (2R)-4,7-dihydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl β-D-glucopyranoside = S-adenosyl-L-homocysteine + (2R)-4-hydroxy-7-methoxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl β-D-glucopyranoside
Glossary: (2R)-4,7-dihydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl β-D-glucopyranoside = TRIMBOA β-D-glucoside
(2R)-4-hydroxy-7-methoxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl β-D-glucopyranoside = DIMBOA β-D-glucoside
Other name(s): BX7 (gene name); OMT BX7
Systematic name: S-adenosyl-L-methionine:(2R)-4,7-dihydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl β-D-glucopyranoside 7-O-methyltransferase
Comments: The enzyme is involved in the biosynthesis of the protective and allelophatic benzoxazinoid DIMBOA [(2R)-4-hydroxy-7-methoxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazin] in some plants, most commonly from the family of Poaceae (grasses).
References:
1.  Jonczyk, R., Schmidt, H., Osterrieder, A., Fiesselmann, A., Schullehner, K., Haslbeck, M., Sicker, D., Hofmann, D., Yalpani, N., Simmons, C., Frey, M. and Gierl, A. Elucidation of the final reactions of DIMBOA-glucoside biosynthesis in maize: characterization of Bx6 and Bx7. Plant Physiol. 146 (2008) 1053–1063. [PMID: 18192444]
[EC 2.1.1.241 created 2012]
 
 
EC 2.1.1.242     
Accepted name: 16S rRNA (guanine1516-N2)-methyltransferase
Reaction: S-adenosyl-L-methionine + guanine1516 in 16S rRNA = S-adenosyl-L-homocysteine + N2-methylguanine1516 in 16S rRNA
Other name(s): yhiQ (gene name); rsmJ (gene name); m2G1516 methyltransferase
Systematic name: S-adenosyl-L-methionine:16S rRNA (guanine1516-N2)-methyltransferase
Comments: The enzyme specifically methylates guanine1516 at N2 in 16S rRNA.
References:
1.  Basturea, G.N., Dague, D.R., Deutscher, M.P. and Rudd, K.E. YhiQ Is RsmJ, the Methyltransferase Responsible for Methylation of G1516 in 16S rRNA of E. coli. J. Mol. Biol. 415 (2012) 16–21. [PMID: 22079366]
[EC 2.1.1.242 created 2012]
 
 
EC 2.1.1.243     
Accepted name: 2-ketoarginine methyltransferase
Reaction: S-adenosyl-L-methionine + 5-guanidino-2-oxopentanoate = S-adenosyl-L-homocysteine + 5-guanidino-3-methyl-2-oxopentanoate
Glossary: 5-guanidino-2-oxopentanoate = 2-ketoarginine
5-guanidino-3-methyl-2-oxopentanoate = 5-carbamimidamido-3-methyl-2-oxopentanoate
Other name(s): mrsA (gene name)
Systematic name: S-adenosyl-L-methionine:5-carbamimidamido-2-oxopentanoate S-methyltransferase
Comments: The enzyme is involved in production of the rare amino acid 3-methylarginine, which is used by the epiphytic bacterium Pseudomonas syringae pv. syringae as an antibiotic against the related pathogenic species Pseudomonas syringae pv. glycinea.
References:
1.  Braun, S.D., Hofmann, J., Wensing, A., Ullrich, M.S., Weingart, H., Völksch, B. and Spiteller, D. Identification of the biosynthetic gene cluster for 3-methylarginine, a toxin produced by Pseudomonas syringae pv. syringae 22d/93. Appl. Environ. Microbiol. 76 (2010) 2500–2508. [PMID: 20190091]
[EC 2.1.1.243 created 2012]
 
 
EC 2.1.1.244     
Accepted name: protein N-terminal methyltransferase
Reaction: (1) 3 S-adenosyl-L-methionine + N-terminal-(A,S)PK-[protein] = 3 S-adenosyl-L-homocysteine + N-terminal-N,N,N-trimethyl-N-(A,S)PK-[protein] (overall reaction)
(1a) S-adenosyl-L-methionine + N-terminal-(A,S)PK-[protein] = S-adenosyl-L-homocysteine + N-terminal-N-methyl-N-(A,S)PK-[protein]
(1b) S-adenosyl-L-methionine + N-terminal-N-methyl-N-(A,S)PK-[protein] = S-adenosyl-L-homocysteine + N-terminal-N,N-dimethyl-N-(A,S)PK-[protein]
(1c) S-adenosyl-L-methionine + N-terminal-N,N-dimethyl-N-(A,S)PK-serine-[protein] = S-adenosyl-L-homocysteine + N-terminal-N,N,N-trimethyl-N-(A,S)PK-[protein]
(2) 2 S-adenosyl-L-methionine + N-terminal-PPK-[protein] = 2 S-adenosyl-L-homocysteine + N-terminal-N,N-dimethyl-N-PPK-[protein] (overall reaction)
(2a) S-adenosyl-L-methionine + N-terminal-PPK-[protein] = S-adenosyl-L-homocysteine + N-terminal-N-methyl-N-PPK-[protein]
(2b) S-adenosyl-L-methionine + N-terminal-N-methyl-N-PPK-[protein] = S-adenosyl-L-homocysteine + N-terminal-N,N-dimethyl-N-PPK-[protein]
Other name(s): NMT1 (gene name); METTL11A (gene name)
Systematic name: S-adenosyl-L-methionine:N-terminal-(A,P,S)PK-[protein] methyltransferase
Comments: This enzyme methylates the N-terminus of target proteins containing the N-terminal motif [Ala/Pro/Ser]-Pro-Lys after the initiator L-methionine is cleaved. When the terminal amino acid is L-proline, the enzyme catalyses two successive methylations of its α-amino group. When the first amino acid is either L-alanine or L-serine, the enzyme catalyses three successive methylations. The Pro-Lys in positions 2-3 cannot be exchanged for other amino acids [1,2].
References:
1.  Webb, K.J., Lipson, R.S., Al-Hadid, Q., Whitelegge, J.P. and Clarke, S.G. Identification of protein N-terminal methyltransferases in yeast and humans. Biochemistry 49 (2010) 5225–5235. [PMID: 20481588]
2.  Tooley, C.E., Petkowski, J.J., Muratore-Schroeder, T.L., Balsbaugh, J.L., Shabanowitz, J., Sabat, M., Minor, W., Hunt, D.F. and Macara, I.G. NRMT is an α-N-methyltransferase that methylates RCC1 and retinoblastoma protein. Nature 466 (2010) 1125–1128. [PMID: 20668449]
[EC 2.1.1.244 created 2012]
 
 
EC 2.1.1.245     
Accepted name: 5-methyltetrahydrosarcinapterin—corrinoid/iron-sulfur protein Co-methyltransferase
Reaction: a [methyl-Co(III) corrinoid Fe-S protein] + tetrahydrosarcinapterin = a [Co(I) corrinoid Fe-S protein] + 5-methyltetrahydrosarcinapterin
Other name(s): cdhD (gene name); cdhE (gene name)
Systematic name: 5-methyltetrahydrosarcinapterin:corrinoid/iron-sulfur protein methyltransferase
Comments: Catalyses the transfer of a methyl group from the cobamide cofactor of a corrinoid/Fe-S protein to the N5 group of tetrahydrosarcinapterin. Forms, together with EC 1.2.7.4, anaerobic carbon-monoxide dehydrogenase, and EC 2.3.1.169, CO-methylating acetyl-CoA synthase, the acetyl-CoA decarbonylase/synthase complex that catalyses the demethylation of acetyl-CoA in a reaction that also forms CO2. This reaction is a key step in methanogenesis from acetate.
References:
1.  Maupin-Furlow, J. and Ferry, J.G. Characterization of the cdhD and cdhE genes encoding subunits of the corrinoid/iron-sulfur enzyme of the CO dehydrogenase complex from Methanosarcina thermophila. J. Bacteriol. 178 (1996) 340–346. [PMID: 8550451]
2.  Grahame, D.A. and DeMoll, E. Partial reactions catalyzed by protein components of the acetyl-CoA decarbonylase synthase enzyme complex from Methanosarcina barkeri. J. Biol. Chem. 271 (1996) 8352–8358. [PMID: 8626532]
[EC 2.1.1.245 created 2012]
 
 
EC 2.1.1.246     
Accepted name: [methyl-Co(III) methanol-specific corrinoid protein]—coenzyme M methyltransferase
Reaction: a [methyl-Co(III) methanol-specific corrinoid protein] + CoM = methyl-CoM + a [Co(I) methanol-specific corrinoid protein]
Glossary: CoM = coenzyme M = 2-mercaptoethanesulfonate
Other name(s): methyltransferase 2 (ambiguous); mtaA (gene name)
Systematic name: methylated methanol-specific corrinoid protein:CoM methyltransferase
Comments: The enzyme, which is involved in methanogenesis from methanol, catalyses the transfer of a methyl group from a corrinoid protein (see EC 2.1.1.90, methanol—corrinoid protein Co-methyltransferase), where it is bound to the cobalt cofactor, to CoM, forming the substrate for EC 2.8.4.1, coenzyme-B sulfoethylthiotransferase, the enzyme that catalyses the final step in methanogenesis. Free methylcob(I)alamin can substitute for the corrinoid protein in vitro [5].
References:
1.  LeClerc, G.M. and Grahame, D.A. Methylcobamide:coenzyme M methyltransferase isozymes from Methanosarcina barkeri. Physicochemical characterization, cloning, sequence analysis, and heterologous gene expression. J. Biol. Chem. 271 (1996) 18725–18731. [PMID: 8702528]
2.  Harms, U. and Thauer, R.K. Methylcobalamin: coenzyme M methyltransferase isoenzymes MtaA and MtbA from Methanosarcina barkeri. Cloning, sequencing and differential transcription of the encoding genes, and functional overexpression of the mtaA gene in Escherichia coli. Eur. J. Biochem. 235 (1996) 653–659. [PMID: 8654414]
3.  Sauer, K. and Thauer, R.K. Methanol:coenzyme M methyltransferase from Methanosarcina barkeri. Zinc dependence and thermodynamics of the methanol:cob(I)alamin methyltransferase reaction. Eur. J. Biochem. 249 (1997) 280–285. [PMID: 9363780]
4.  Sauer, K., Harms, U. and Thauer, R.K. Methanol:coenzyme M methyltransferase from Methanosarcina barkeri. Purification, properties and encoding genes of the corrinoid protein MT1. Eur. J. Biochem. 243 (1997) 670–677. [PMID: 9057830]
5.  Sauer, K. and Thauer, R.K. Methanol:coenzyme M methyltransferase from Methanosarcina barkeri – substitution of the corrinoid harbouring subunit MtaC by free cob(I)alamin. Eur. J. Biochem. 261 (1999) 674–681. [PMID: 10215883]
[EC 2.1.1.246 created 2012]
 
 
EC 2.1.1.247     
Accepted name: [methyl-Co(III) methylamine-specific corrinoid protein]—coenzyme M methyltransferase
Reaction: a [methyl-Co(III) methylamine-specific corrinoid protein] + CoM = methyl-CoM + a [Co(I) methylamine-specific corrinoid protein]
Glossary: CoM = coenzyme M = 2-mercaptoethanesulfonate
Other name(s): methyltransferase 2 (ambiguous); MT2 (ambiguous); MT2-A; mtbA (gene name); [methyl-Co(III) methylamine-specific corrinoid protein]:coenzyme M methyltransferase
Systematic name: methylated monomethylamine-specific corrinoid protein:CoM methyltransferase
Comments: Contains zinc [2]. The enzyme, which is involved in methanogenesis from mono-, di-, and trimethylamine, catalyses the transfer of a methyl group bound to the cobalt cofactor of several corrinoid proteins (mono-, di-, and trimethylamine-specific corrinoid proteins, cf. EC 2.1.1.248, methylamine—corrinoid protein Co-methyltransferase, EC 2.1.1.249, dimethylamine—corrinoid protein Co-methyltransferase, and EC 2.1.1.250, trimethylamine—corrinoid protein Co-methyltransferase) to CoM, forming the substrate for EC 2.8.4.1, coenzyme-B sulfoethylthiotransferase, the enzyme that catalyses the final step in methanogenesis.
References:
1.  Burke, S.A. and Krzycki, J.A. Involvement of the "A" isozyme of methyltransferase II and the 29-kilodalton corrinoid protein in methanogenesis from monomethylamine. J. Bacteriol. 177 (1995) 4410–4416. [PMID: 7635826]
2.  LeClerc, G.M. and Grahame, D.A. Methylcobamide:coenzyme M methyltransferase isozymes from Methanosarcina barkeri. Physicochemical characterization, cloning, sequence analysis, and heterologous gene expression. J. Biol. Chem. 271 (1996) 18725–18731. [PMID: 8702528]
3.  Ferguson, D.J., Jr. and Krzycki, J.A. Reconstitution of trimethylamine-dependent coenzyme M methylation with the trimethylamine corrinoid protein and the isozymes of methyltransferase II from Methanosarcina barkeri. J. Bacteriol. 179 (1997) 846–852. [PMID: 9006042]
4.  Burke, S.A., Lo, S.L. and Krzycki, J.A. Clustered genes encoding the methyltransferases of methanogenesis from monomethylamine. J. Bacteriol. 180 (1998) 3432–3440. [PMID: 9642198]
5.  Ferguson, D.J., Jr., Gorlatova, N., Grahame, D.A. and Krzycki, J.A. Reconstitution of dimethylamine:coenzyme M methyl transfer with a discrete corrinoid protein and two methyltransferases purified from Methanosarcina barkeri. J. Biol. Chem. 275 (2000) 29053–29060. [PMID: 10852929]
[EC 2.1.1.247 created 2012]
 
 
EC 2.1.1.248     
Accepted name: methylamine—corrinoid protein Co-methyltransferase
Reaction: methylamine + a [Co(I) methylamine-specific corrinoid protein] = a [methyl-Co(III) methylamine-specific corrinoid protein] + NH3
Other name(s): mtmB (gene name); monomethylamine methyltransferase
Systematic name: monomethylamine:5-hydroxybenzimidazolylcobamide Co-methyltransferase
Comments: The enzyme, which catalyses the transfer of a methyl group from methylamine to a methylamine-specific corrinoid protein (MtmC), is involved in methanogenesis from methylamine. The enzyme contains the unusual amino acid pyrrolysine [3]. Methylation of the corrinoid protein requires the central cobalt to be in the Co(I) state. During methylation the cobalt is oxidized to the Co(III) state. The methylated corrinoid protein is substrate for EC 2.1.1.247, methylated methylamine-specific corrinoid protein:coenzyme M methyltransferase.
References:
1.  Burke, S.A. and Krzycki, J.A. Reconstitution of Monomethylamine:Coenzyme M methyl transfer with a corrinoid protein and two methyltransferases purified from Methanosarcina barkeri. J. Biol. Chem. 272 (1997) 16570–16577. [PMID: 9195968]
2.  Burke, S.A., Lo, S.L. and Krzycki, J.A. Clustered genes encoding the methyltransferases of methanogenesis from monomethylamine. J. Bacteriol. 180 (1998) 3432–3440. [PMID: 9642198]
3.  Krzycki, J.A. Function of genetically encoded pyrrolysine in corrinoid-dependent methylamine methyltransferases. Curr. Opin. Chem. Biol. 8 (2004) 484–491. [PMID: 15450490]
[EC 2.1.1.248 created 2012]
 
 
EC 2.1.1.249     
Accepted name: dimethylamine—corrinoid protein Co-methyltransferase
Reaction: dimethylamine + a [Co(I) dimethylamine-specific corrinoid protein] = a [methyl-Co(III) dimethylamine-specific corrinoid protein] + methylamine
Other name(s): mtbB (gene name); dimethylamine methyltransferase
Systematic name: dimethylamine:5-hydroxybenzimidazolylcobamide Co-methyltransferase
Comments: The enzyme, which catalyses the transfer of a methyl group from dimethylamine to a dimethylamine-specific corrinoid protein (MtbC), is involved in methanogenesis from dimethylamine. The enzyme contains the unusual amino acid pyrrolysine [3]. Methylation of the corrinoid protein requires the central cobalt to be in the Co(I) state. During methylation the cobalt is oxidized to the Co(III) state. The methylated corrinoid protein is substrate for EC 2.1.1.247, methylated methylamine-specific corrinoid protein:coenzyme M methyltransferase.
References:
1.  Wassenaar, R.W., Keltjens, J.T., van der Drift, C. and Vogels, G.D. Purification and characterization of dimethylamine:5-hydroxybenzimidazolyl-cobamide methyltransferase from Methanosarcina barkeri Fusaro. Eur. J. Biochem. 253 (1998) 692–697. [PMID: 9654067]
2.  Ferguson, D.J., Jr., Gorlatova, N., Grahame, D.A. and Krzycki, J.A. Reconstitution of dimethylamine:coenzyme M methyl transfer with a discrete corrinoid protein and two methyltransferases purified from Methanosarcina barkeri. J. Biol. Chem. 275 (2000) 29053–29060. [PMID: 10852929]
3.  Krzycki, J.A. Function of genetically encoded pyrrolysine in corrinoid-dependent methylamine methyltransferases. Curr. Opin. Chem. Biol. 8 (2004) 484–491. [PMID: 15450490]
[EC 2.1.1.249 created 2012]
 
 
EC 2.1.1.250     
Accepted name: trimethylamine—corrinoid protein Co-methyltransferase
Reaction: trimethylamine + a [Co(I) trimethylamine-specific corrinoid protein] = a [methyl-Co(III) trimethylamine-specific corrinoid protein] + dimethylamine
Other name(s): mttB (gene name); trimethylamine methyltransferase
Systematic name: trimethylamine:5-hydroxybenzimidazolylcobamide Co-methyltransferase
Comments: The enzyme, which catalyses the transfer of a methyl group from trimethylamine to a trimethylamine-specific corrinoid protein (MttC), is involved in methanogenesis from trimethylamine. The enzyme contains the unusual amino acid pyrrolysine [2]. Methylation of the corrinoid protein requires the central cobalt to be in the Co(I) state. During methylation the cobalt is oxidized to the Co(III) state. The methylated corrinoid protein is substrate for EC 2.1.1.247, methylated methylamine-specific corrinoid protein:coenzyme M methyltransferase.
References:
1.  Ferguson, D.J., Jr. and Krzycki, J.A. Reconstitution of trimethylamine-dependent coenzyme M methylation with the trimethylamine corrinoid protein and the isozymes of methyltransferase II from Methanosarcina barkeri. J. Bacteriol. 179 (1997) 846–852. [PMID: 9006042]
2.  Krzycki, J.A. Function of genetically encoded pyrrolysine in corrinoid-dependent methylamine methyltransferases. Curr. Opin. Chem. Biol. 8 (2004) 484–491. [PMID: 15450490]
[EC 2.1.1.250 created 2012]
 
 
EC 2.1.1.251     
Accepted name: methylated-thiol—coenzyme M methyltransferase
Reaction: methanethiol + CoM = methyl-CoM + hydrogen sulfide (overall reaction)
(1a) methanethiol + a [Co(I) methylated-thiol-specific corrinoid protein] = a [methyl-Co(III) methylated-thiol-specific corrinoid protein] + hydrogen sulfide
(1b) a [methyl-Co(III) methylated-thiol-specific corrinoid protein] + CoM = methyl-CoM + a [Co(I) methylated-thiol-specific corrinoid protein]
Glossary: CoM = coenzyme M = 2-mercaptoethanesulfonate
Other name(s): mtsA (gene name)
Systematic name: methylated-thiol:CoM methyltransferase
Comments: The enzyme, which is involved in methanogenesis from methylated thiols, such as methane thiol, dimethyl sulfide, and 3-S-methylmercaptopropionate, catalyses two successive steps - the transfer of a methyl group from the substrate to the cobalt cofactor of a methylated-thiol-specific corrinoid protein (MtsB), and the subsequent transfer of the methyl group from the corrinoid protein to CoM. With most other methanogenesis substrates this process is carried out by two different enzymes (for example, EC 2.1.1.90, methanol—corrinoid protein Co-methyltransferase, and EC 2.1.1.246, methylated methanol-specific corrinoid protein:coenzyme M methyltransferase). The cobalt is oxidized during methylation from the Co(I) state to the Co(III) state, and is reduced back to the Co(I) form during demethylation.
References:
1.  Paul, L. and Krzycki, J.A. Sequence and transcript analysis of a novel Methanosarcina barkeri methyltransferase II homolog and its associated corrinoid protein homologous to methionine synthase. J. Bacteriol. 178 (1996) 6599–6607. [PMID: 8932317]
2.  Tallant, T.C. and Krzycki, J.A. Methylthiol:coenzyme M methyltransferase from Methanosarcina barkeri, an enzyme of methanogenesis from dimethylsulfide and methylmercaptopropionate. J. Bacteriol. 179 (1997) 6902–6911. [PMID: 9371433]
3.  Tallant, T.C., Paul, L. and Krzycki, J.A. The MtsA subunit of the methylthiol:coenzyme M methyltransferase of Methanosarcina barkeri catalyses both half-reactions of corrinoid-dependent dimethylsulfide: coenzyme M methyl transfer. J. Biol. Chem. 276 (2001) 4485–4493. [PMID: 11073950]
[EC 2.1.1.251 created 2012]
 
 
EC 2.1.1.252     
Accepted name: tetramethylammonium—corrinoid protein Co-methyltransferase
Reaction: tetramethylammonium + a [Co(I) tetramethylammonium-specific corrinoid protein] = a [methyl-Co(III) tetramethylammonium-specific corrinoid protein] + trimethylamine
Other name(s): mtqB (gene name); tetramethylammonium methyltransferase
Systematic name: tetramethylammonium:5-hydroxybenzimidazolylcobamide Co-methyltransferase
Comments: The enzyme, which catalyses the transfer of a methyl group from tetramethylammonium to a tetramethylammonium-specific corrinoid protein (MtqC), is involved in methanogenesis from tetramethylammonium. Methylation of the corrinoid protein requires the central cobalt to be in the Co(I) state. During methylation the cobalt is oxidized to the Co(III) state. The methylated corrinoid protein is substrate for EC 2.1.1.253, methylated tetramethylammonium-specific corrinoid protein:coenzyme M methyltransferase.
References:
1.  Asakawa, S., Sauer, K., Liesack, W. and Thauer, R.K. Tetramethylammonium:coenzyme M methyltransferase system from methanococcoides s. Arch. Microbiol. 170 (1998) 220–226. [PMID: 9732435]
[EC 2.1.1.252 created 2012]
 
 
EC 2.1.1.253     
Accepted name: [methyl-Co(III) tetramethylammonium-specific corrinoid protein]—coenzyme M methyltransferase
Reaction: a [methyl-Co(III) tetramethylammonium-specific corrinoid protein] + CoM = methyl-CoM + a [Co(I) tetramethylammonium-specific corrinoid protein]
Glossary: CoM = coenzyme M = 2-mercaptoethanesulfonate
Other name(s): methyltransferase 2 (ambiguous); mtqA (gene name)
Systematic name: methylated tetramethylammonium-specific corrinoid protein:CoM methyltransferase
Comments: The enzyme, which is involved in methanogenesis from tetramethylammonium, catalyses the transfer of a methyl group from a corrinoid protein (see EC 2.1.1.252, tetramethylammonium—corrinoid protein Co-methyltransferase), where it is bound to the cobalt cofactor, to CoM, forming the substrate for EC 2.8.4.1, coenzyme-B sulfoethylthiotransferase, the enzyme that catalyses the final step in methanogenesis.
References:
1.  Asakawa, S., Sauer, K., Liesack, W. and Thauer, R.K. Tetramethylammonium:coenzyme M methyltransferase system from methanococcoides s. Arch. Microbiol. 170 (1998) 220–226. [PMID: 9732435]
[EC 2.1.1.253 created 2012]
 
 
EC 2.1.1.254     
Accepted name: erythromycin 3′′-O-methyltransferase
Reaction: (1) S-adenosyl-L-methionine + erythromycin C = S-adenosyl-L-homocysteine + erythromycin A
(2) S-adenosyl-L-methionine + erythromycin D = S-adenosyl-L-homocysteine + erythromycin B
Other name(s): EryG
Systematic name: S-adenosyl-L-methionine:erythromycin C 3′′-O-methyltransferase
Comments: The enzyme methylates the 3 position of the mycarosyl moiety of erythromycin C, forming the most active form of the antibiotic, erythromycin A. It can also methylate the precursor erythromycin D, forming erythromycin B, which is then converted to erythromycin A by EC 1.14.13.154, erythromycin 12 hydroxylase.
References:
1.  Paulus, T.J., Tuan, J.S., Luebke, V.E., Maine, G.T., DeWitt, J.P. and Katz, L. Mutation and cloning of eryG, the structural gene for erythromycin O-methyltransferase from Saccharopolyspora erythraea, and expression of eryG in Escherichia coli. J. Bacteriol. 172 (1990) 2541–2546. [PMID: 2185226]
2.  Summers, R.G., Donadio, S., Staver, M.J., Wendt-Pienkowski, E., Hutchinson, C.R. and Katz, L. Sequencing and mutagenesis of genes from the erythromycin biosynthetic gene cluster of Saccharopolyspora erythraea that are involved in L-mycarose and D-desosamine production. Microbiology 143 (1997) 3251–3262. [PMID: 9353926]
[EC 2.1.1.254 created 2012]
 
 
EC 2.1.1.255     
Accepted name: geranyl diphosphate 2-C-methyltransferase
Reaction: S-adenosyl-L-methionine + geranyl diphosphate = S-adenosyl-L-homocysteine + (E)-2-methylgeranyl diphosphate
Other name(s): SCO7701; GPP methyltransferase; GPPMT; 2-methyl-GPP synthase; MGPPS; geranyl pyrophosphate methyltransferase
Systematic name: S-adenosyl-L-methionine:geranyl-diphosphate 2-C-methyltransferase
Comments: This enzyme, along with EC 4.2.3.118, 2-methylisoborneol synthase, produces 2-methylisoborneol, an odiferous compound produced by soil microorganisms with a strong earthy/musty odour.
References:
1.  Wang, C.M. and Cane, D.E. Biochemistry and molecular genetics of the biosynthesis of the earthy odorant methylisoborneol in Streptomyces coelicolor. J. Am. Chem. Soc. 130 (2008) 8908–8909. [PMID: 18563898]
2.  Ariyawutthiphan, O., Ose, T., Tsuda, M., Gao, Y., Yao, M., Minami, A., Oikawa, H. and Tanaka, I. Crystallization and preliminary X-ray crystallographic study of a methyltransferase involved in 2-methylisoborneol biosynthesis in Streptomyces lasaliensis. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 67 (2011) 417–420. [PMID: 21393856]
3.  Komatsu, M., Tsuda, M., Omura, S., Oikawa, H. and Ikeda, H. Identification and functional analysis of genes controlling biosynthesis of 2-methylisoborneol. Proc. Natl. Acad. Sci. USA 105 (2008) 7422–7427. [PMID: 18492804]
4.  Giglio, S., Chou, W.K., Ikeda, H., Cane, D.E. and Monis, P.T. Biosynthesis of 2-methylisoborneol in cyanobacteria. Environ. Sci. Technol. 45 (2011) 992–998. [PMID: 21174459]
[EC 2.1.1.255 created 2012]
 
 
EC 2.1.1.256     
Accepted name: tRNA (guanine6-N2)-methyltransferase
Reaction: S-adenosyl-L-methionine + guanine6 in tRNA = S-adenosyl-L-homocysteine + N2-methylguanine6 in tRNA
Other name(s): methyltransferase Trm14; m2G6 methyltransferase
Systematic name: S-adenosyl-L-methionine:tRNA (guanine6-N2)-methyltransferase
Comments: The enzyme specifically methylates guanine6 at N2 in tRNA.
References:
1.  Menezes, S., Gaston, K.W., Krivos, K.L., Apolinario, E.E., Reich, N.O., Sowers, K.R., Limbach, P.A. and Perona, J.J. Formation of m2G6 in Methanocaldococcus jannaschii tRNA catalyzed by the novel methyltransferase Trm14. Nucleic Acids Res. 39 (2011) 7641–7655. [PMID: 21693558]
[EC 2.1.1.256 created 2012]
 
 
EC 2.1.1.257     
Accepted name: tRNA (pseudouridine54-N1)-methyltransferase
Reaction: S-adenosyl-L-methionine + pseudouridine54 in tRNA = S-adenosyl-L-homocysteine + N1-methylpseudouridine54 in tRNA
Other name(s): TrmY; m1Ψ methyltransferase
Systematic name: S-adenosyl-L-methionine:tRNA (pseudouridine54-N1)-methyltransferase
Comments: While this archaeal enzyme is specific for the 54 position and does not methylate pseudouridine at position 55, the presence of pseudouridine at position 55 is necessary for the efficient methylation of pseudouridine at position 54 [2,3].
References:
1.  Chen, H.Y. and Yuan, Y.A. Crystal structure of Mj1640/DUF358 protein reveals a putative SPOUT-class RNA methyltransferase. J. Mol. Cell. Biol. 2 (2010) 366–374. [PMID: 21098051]
2.  Wurm, J.P., Griese, M., Bahr, U., Held, M., Heckel, A., Karas, M., Soppa, J. and Wohnert, J. Identification of the enzyme responsible for N1-methylation of pseudouridine 54 in archaeal tRNAs. RNA 18 (2012) 412–420. [PMID: 22274954]
3.  Chatterjee, K., Blaby, I.K., Thiaville, P.C., Majumder, M., Grosjean, H., Yuan, Y.A., Gupta, R. and de Crecy-Lagard, V. The archaeal COG1901/DUF358 SPOUT-methyltransferase members, together with pseudouridine synthase Pus10, catalyze the formation of 1-methylpseudouridine at position 54 of tRNA. RNA 18 (2012) 421–433. [PMID: 22274953]
[EC 2.1.1.257 created 2012]
 
 
EC 2.1.1.258     
Accepted name: 5-methyltetrahydrofolate—corrinoid/iron-sulfur protein Co-methyltransferase
Reaction: a [methyl-Co(III) corrinoid Fe-S protein] + tetrahydrofolate = a [Co(I) corrinoid Fe-S protein] + 5-methyltetrahydrofolate
Other name(s): acsE (gene name)
Systematic name: 5-methyltetrahydrofolate:corrinoid/iron-sulfur protein methyltransferase
Comments: Catalyses the transfer of a methyl group from the N5 group of methyltetrahydrofolate to the 5-methoxybenzimidazolylcobamide cofactor of a corrinoid/Fe-S protein. Involved, together with EC 1.2.7.4, anaerobic carbon-monoxide dehydrogenase and EC 2.3.1.169, CO-methylating acetyl-CoA synthase, in the reductive acetyl coenzyme A (Wood-Ljungdahl) pathway of autotrophic carbon fixation in various bacteria and archaea.
References:
1.  Roberts, D.L., Zhao, S., Doukov, T. and Ragsdale, S.W. The reductive acetyl coenzyme A pathway: sequence and heterologous expression of active methyltetrahydrofolate:corrinoid/iron-sulfur protein methyltransferase from Clostridium thermoaceticum. J. Bacteriol. 176 (1994) 6127–6130. [PMID: 7928975]
2.  Doukov, T., Seravalli, J., Stezowski, J.J. and Ragsdale, S.W. Crystal structure of a methyltetrahydrofolate- and corrinoid-dependent methyltransferase. Structure 8 (2000) 817–830. [PMID: 10997901]
3.  Doukov, T.I., Hemmi, H., Drennan, C.L. and Ragsdale, S.W. Structural and kinetic evidence for an extended hydrogen-bonding network in catalysis of methyl group transfer. Role of an active site asparagine residue in activation of methyl transfer by methyltransferases. J. Biol. Chem. 282 (2007) 6609–6618. [PMID: 17172470]
[EC 2.1.1.258 created 2012]
 
 
EC 2.1.1.259     
Accepted name: [fructose-bisphosphate aldolase]-lysine N-methyltransferase
Reaction: 3 S-adenosyl-L-methionine + [fructose-bisphosphate aldolase]-L-lysine = 3 S-adenosyl-L-homocysteine + [fructose-bisphosphate aldolase]-N6,N6,N6-trimethyl-L-lysine
Other name(s): rubisco methyltransferase; ribulose-bisphosphate-carboxylase/oxygenase N-methyltransferase; ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit εN-methyltransferase; S-adenosyl-L-methionine:[3-phospho-D-glycerate-carboxy-lyase (dimerizing)]-lysine 6-N-methyltransferase
Systematic name: S-adenosyl-L-methionine:[fructose-bisphosphate aldolase]-lysine N6-methyltransferase
Comments: The enzyme methylates a conserved lysine in the C-terminal part of higher plant fructose-bisphosphate aldolase (EC 4.1.2.13). The enzyme from pea (Pisum sativum) also methylates Lys-14 in the large subunits of hexadecameric higher plant ribulose-bisphosphate-carboxylase (EC 4.1.1.39) [2], but that from Arabidopsis thaliana does not.
References:
1.  Magnani, R., Nayak, N.R., Mazarei, M., Dirk, L.M. and Houtz, R.L. Polypeptide substrate specificity of PsLSMT. A set domain protein methyltransferase. J. Biol. Chem. 282 (2007) 27857–27864. [PMID: 17635932]
2.  Mininno, M., Brugiere, S., Pautre, V., Gilgen, A., Ma, S., Ferro, M., Tardif, M., Alban, C. and Ravanel, S. Characterization of chloroplastic fructose 1,6-bisphosphate aldolases as lysine-methylated proteins in plants. J. Biol. Chem. 287 (2012) 21034–21044. [PMID: 22547063]
[EC 2.1.1.259 created 2012]
 
 
EC 2.1.1.260     
Accepted name: rRNA small subunit pseudouridine methyltransferase Nep1
Reaction: S-adenosyl-L-methionine + pseudouridine1191 in yeast 18S rRNA = S-adenosyl-L-homocysteine + N1-methylpseudouridine1191 in yeast 18S rRNA
Other name(s): Nep1; nucleolar essential protein 1
Systematic name: S-adenosyl-L-methionine:18S rRNA (pseudouridine1191-N1)-methyltransferase
Comments: This enzyme, which occurs in both prokaryotes and eukaryotes, recognizes specific pseudouridine residues (Ψ) in small subunits of ribosomal RNA based on the local RNA structure. It recognizes Ψ914 in 16S rRNA from the archaeon Methanocaldococcus jannaschii, Ψ1191 in yeast 18S rRNA, and Ψ1248 in human 18S rRNA.
References:
1.  Taylor, A.B., Meyer, B., Leal, B.Z., Kötter, P., Schirf, V., Demeler, B., Hart, P.J., Entian, K.-D. and Wöhnert, J. The crystal structure of Nep1 reveals an extended SPOUT-class methyltransferase fold and a pre-organized SAM-binding site. Nucleic Acids Res. 36 (2008) 1542–1554. [PMID: 18208838]
2.  Wurm, J.P., Meyer, B., Bahr, U., Held, M., Frolow, O., Kötter, P., Engels, J.W., Heckel, A., Karas, M., Entian, K.-D. and Wöhnert, J. The ribosome assembly factor Nep1 responsible for Bowen-Conradi syndrome is a pseudouridine-N1-specific methyltransferase. Nucleic Acids Res. 38 (2010) 2387–2398. [PMID: 20047967]
3.  Meyer, B., Wurm, J.P., Kötter, P., Leisegang, M.S., Schilling, V., Buchhaupt, M., Held, M., Bahr, U., Karas, M., Heckel, A., Bohnsack, M.T., Wöhnert, J. and Entian, K.-D. The Bowen-Conradi syndrome protein Nep1 (Emg1) has a dual role in eukaryotic ribosome biogenesis, as an essential assembly factor and in the methylation of Ψ1191 in yeast 18S rRNA. Nucleic Acids Res. 39 (2011) 1526–1537. [PMID: 20972225]
[EC 2.1.1.260 created 2012]
 
 
EC 2.1.1.261     
Accepted name: 4-dimethylallyltryptophan N-methyltransferase
Reaction: S-adenosyl-L-methionine + 4-dimethylallyl-L-tryptophan = S-adenosyl-L-homocysteine + 4-dimethylallyl-L-abrine
Glossary: 4-dimethylallyl-L-tryptophan = 4-(3-methylbut-2-enyl)-L-tryptophan;
4-dimethylallyl-L-abrine = 4-(3-methylbut-2-enyl)-L-abrine
Other name(s): fgaMT (gene name); easF (gene name)
Systematic name: S-adenosyl-L-methionine:4-(3-methylbut-2-enyl)-L-tryptophan N-methyltransferase
Comments: The enzyme catalyses a step in the pathway leading to biosynthesis of ergot alkaloids in certain fungi.
References:
1.  Rigbers, O. and Li, S.M. Ergot alkaloid biosynthesis in Aspergillus fumigatus. Overproduction and biochemical characterization of a 4-dimethylallyltryptophan N-methyltransferase. J. Biol. Chem. 283 (2008) 26859–26868. [PMID: 18678866]
[EC 2.1.1.261 created 2012]
 
 
EC 2.1.1.262     
Accepted name: squalene methyltransferase
Reaction: 2 S-adenosyl-L-methionine + squalene = 2 S-adenosyl-L-homocysteine + 3,22-dimethyl-1,2,23,24-tetradehydro-2,3,22,23-tetrahydrosqualene (overall reaction)
(1a) S-adenosyl-L-methionine + squalene = S-adenosyl-L-homocysteine + 3-methyl-1,2-didehydro-2,3-dihydrosqualene
(1b) S-adenosyl-L-methionine + 3-methyl-1,2-didehydro-2,3-dihydrosqualene = S-adenosyl-L-homocysteine + 3,22-dimethyl-1,2,23,24-tetradehydro-2,3,22,23-tetrahydrosqualene
Other name(s): TMT-1; TMT-2
Systematic name: S-adenosyl-L-methionine:squalene C-methyltransferase
Comments: Two isoforms differing in their specificity were isolated from the green alga Botryococcus braunii BOT22. TMT-1 gave more of the dimethylated form whereas TMT2 gave more of the monomethylated form.
References:
1.  Niehaus, T.D., Kinison, S., Okada, S., Yeo, Y.S., Bell, S.A., Cui, P., Devarenne, T.P. and Chappell, J. Functional identification of triterpene methyltransferases from Botryococcus braunii race B. J. Biol. Chem. 287 (2012) 8163–8173. [PMID: 22241476]
[EC 2.1.1.262 created 2012]
 
 
EC 2.1.1.263     
Accepted name: botryococcene C-methyltransferase
Reaction: 2 S-adenosyl-L-methionine + C30 botryococcene = 2 S-adenosyl-L-homocysteine + 3,20-dimethyl-1,2,21,22-tetradehydro-2,3,20,21-tetrahydrobotryococcene (overall reaction)
(1a) S-adenosyl-L-methionine + C30 botryococcene = S-adenosyl-L-homocysteine + 3-methyl-1,2-didehydro-2,3-dihydrobotryococcene
(1b) S-adenosyl-L-methionine + 3-methyl-1,2-didehydro-2,3-dihydrobotryococcene = S-adenosyl-L-homocysteine + 3,20-dimethyl-1,2,21,22-tetradehydro-2,3,20,21-tetrahydrobotryococcene
(2a) S-adenosyl-L-methionine + C30 botryococcene = S-adenosyl-L-homocysteine + 20-methyl-21,22-didehydro-20,21-dihydrobotryococcene
(2b) S-adenosyl-L-methionine + 20-methyl-21,22-didehydro-20,21-dihydrobotryococcene = S-adenosyl-L-homocysteine + 3,20-dimethyl-1,2,21,22-tetradehydro-2,3,20,21-tetrahydrobotryococcene
Glossary: C30 botryococcene = (10S,13R)-10-ethenyl-2,6,10,13,17,21-hexamethyldocosa-2,5,11,16,20-pentaene
3-methyl-1,2-didehydro-2,3-dihydrobotryococcene = showacene
20-methyl-21,22-didehydro-20,21-dihydrobotryococcene = isoshowacene
Other name(s): TMT-3
Systematic name: S-adenosyl-L-methionine:botryococcene C-methyltransferase
Comments: Isolated from the green alga Botryococcus braunii BOT22. Shows a very weak activity with squalene.
References:
1.  Niehaus, T.D., Kinison, S., Okada, S., Yeo, Y.S., Bell, S.A., Cui, P., Devarenne, T.P. and Chappell, J. Functional identification of triterpene methyltransferases from Botryococcus braunii race B. J. Biol. Chem. 287 (2012) 8163–8173. [PMID: 22241476]
[EC 2.1.1.263 created 2012]
 
 
EC 2.1.1.264     
Accepted name: 23S rRNA (guanine2069-N7)-methyltransferase
Reaction: S-adenosyl-L-methionine + guanine2069 in 23S rRNA = S-adenosyl-L-homocysteine + N7-methylguanine2069 in 23S rRNA
Other name(s): rlmK (gene name); 23S rRNA m7G2069 methyltransferase
Systematic name: S-adenosyl-L-methionine:23S rRNA (guanine2069-N7)-methyltransferase
Comments: The enzyme specifically methylates guanine2069 at position N7 in 23S rRNA. In γ-proteobacteria the enzyme also catalyses EC 2.1.1.173, 23S rRNA (guanine2445-N2)-methyltransferase, while in β-proteobacteria the activities are carried out by separate proteins [1]. The enzyme from the γ-proteobacterium Escherichia coli has RNA unwinding activity as well [1].
References:
1.  Kimura, S., Ikeuchi, Y., Kitahara, K., Sakaguchi, Y., Suzuki, T. and Suzuki, T. Base methylations in the double-stranded RNA by a fused methyltransferase bearing unwinding activity. Nucleic Acids Res. 40 (2012) 4071–4085. [PMID: 22210896]
[EC 2.1.1.264 created 2012]
 
 
EC 2.1.1.265     
Accepted name: tellurite methyltransferase
Reaction: S-adenosyl-L-methionine + tellurite = S-adenosyl-L-homocysteine + methanetelluronate
Other name(s): TehB
Systematic name: S-adenosyl-L-methionine:tellurite methyltransferase
Comments: The enzyme is involved in the detoxification of tellurite. It can also methylate selenite and selenium dioxide.
References:
1.  Liu, M., Turner, R.J., Winstone, T.L., Saetre, A., Dyllick-Brenzinger, M., Jickling, G., Tari, L.W., Weiner, J.H. and Taylor, D.E. Escherichia coli TehB requires S-adenosylmethionine as a cofactor to mediate tellurite resistance. J. Bacteriol. 182 (2000) 6509–6513. [PMID: 11053398]
2.  Choudhury, H.G., Cameron, A.D., Iwata, S. and Beis, K. Structure and mechanism of the chalcogen-detoxifying protein TehB from Escherichia coli. Biochem. J. 435 (2011) 85–91. [PMID: 21244361]
[EC 2.1.1.265 created 2012]
 
 
EC 2.1.1.266     
Accepted name: 23S rRNA (adenine2030-N6)-methyltransferase
Reaction: S-adenosyl-L-methionine + adenine2030 in 23S rRNA = S-adenosyl-L-homocysteine + N6-methyladenine2030 in 23S rRNA
Other name(s): YhiR protein; rlmJ (gene name); m6A2030 methyltransferase
Systematic name: S-adenosyl-L-methionine:23S rRNA (adenine2030-N6)-methyltransferase
Comments: The recombinant RlmJ protein is most active in methylating deproteinized 23S ribosomal subunit, and does not methylate the completely assembled 50S subunits [1].
References:
1.  Golovina, A.Y., Dzama, M.M., Osterman, I.A., Sergiev, P.V., Serebryakova, M.V., Bogdanov, A.A. and Dontsova, O.A. The last rRNA methyltransferase of E. coli revealed: the yhiR gene encodes adenine-N6 methyltransferase specific for modification of A2030 of 23S ribosomal RNA. RNA 18 (2012) 1725–1734. [PMID: 22847818]
[EC 2.1.1.266 created 2013]
 
 
EC 2.1.1.267     
Accepted name: flavonoid 3′,5′-methyltransferase
Reaction: (1) S-adenosyl-L-methionine + a 3′-hydroxyflavonoid = S-adenosyl-L-homocysteine + a 3′-methoxyflavonoid
(2) S-adenosyl-L-methionine + a 5′-hydroxy-3′-methoxyflavonoid = S-adenosyl-L-homocysteine + a 3′,5′-dimethoxyflavonoid
Glossary: delphinidin = 3,3′,4′,5,5′,7-hexahydroxyflavylium
cyanidin = 3,3′,4′,5,7-pentahydroxyflavylium
myricetin = 3,3′,4′,5,5′,7-hexahydroxyflavone
quercetin = 3,3′,4′,5,7-pentahydroxyflavone
Other name(s): AOMT; CrOMT2
Systematic name: S-adenosyl-L-methionine:flavonoid 3′-O-methyltransferase
Comments: Isolated from Vitis vinifera (grape) [2]. Most active with delphinidin 3-glucoside but also acts on cyanidin 3-glucoside, cyanidin, myricetin, quercetin and quercetin 3-glucoside. The enzyme from Catharanthus roseus was most active with myricetin [1].
References:
1.  Cacace, S., Schröder, G., Wehinger, E., Strack, D., Schmidt, J. and Schröder, J. A flavonol O-methyltransferase from Catharanthus roseus performing two sequential methylations. Phytochemistry 62 (2003) 127–137. [PMID: 12482447]
2.  Hugueney, P., Provenzano, S., Verries, C., Ferrandino, A., Meudec, E., Batelli, G., Merdinoglu, D., Cheynier, V., Schubert, A. and Ageorges, A. A novel cation-dependent O-methyltransferase involved in anthocyanin methylation in grapevine. Plant Physiol. 150 (2009) 2057–2070. [PMID: 19525322]
[EC 2.1.1.267 created 2013, modified 2014]
 
 
EC 2.1.1.268     
Accepted name: tRNAThr (cytosine32-N3)-methyltransferase
Reaction: (1) S-adenosyl-L-methionine + cytosine32 in tRNAThr = S-adenosyl-L-homocysteine + N3-methylcytosine32 in tRNAThr
(2) S-adenosyl-L-methionine + cytosine32 in tRNASer = S-adenosyl-L-homocysteine + N3-methylcytosine32 in tRNASer
Other name(s): ABP140; Trm140p
Systematic name: S-adenosyl-L-methionine:tRNAThr (cytosine32-N3)-methyltransferase
Comments: The enzyme from Saccharomyces cerevisiae specifically methylates cytosine32 in tRNAThr and in tRNASer.
References:
1.  Noma, A., Yi, S., Katoh, T., Takai, Y., Suzuki, T. and Suzuki, T. Actin-binding protein ABP140 is a methyltransferase for 3-methylcytidine at position 32 of tRNAs in Saccharomyces cerevisiae. RNA 17 (2011) 1111–1119. [PMID: 21518805]
2.  D'Silva, S., Haider, S.J. and Phizicky, E.M. A domain of the actin binding protein Abp140 is the yeast methyltransferase responsible for 3-methylcytidine modification in the tRNA anti-codon loop. RNA 17 (2011) 1100–1110. [PMID: 21518804]
[EC 2.1.1.268 created 2013]
 
 
EC 2.1.1.269     
Accepted name: dimethylsulfoniopropionate demethylase
Reaction: S,S-dimethyl-β-propiothetin + tetrahydrofolate = 3-(methylsulfanyl)propanoate + 5-methyltetrahydrofolate
Glossary: S,S-dimethyl-β-propiothetin = 3-(S,S-dimethylsulfonio)propanoate
Other name(s): dmdA (gene name); dimethylsulfoniopropionate-dependent demethylase A
Systematic name: S,S-dimethyl-β-propiothetin:tetrahydrofolate S-methyltransferase
Comments: The enzyme from the marine bacteria Pelagibacter ubique and Ruegeria pomeroyi are specific towards S,S-dimethyl-β-propiothetin. They do not demethylate glycine-betaine [1,2].
References:
1.  Jansen, M. and Hansen, T.A. Tetrahydrofolate serves as a methyl acceptor in the demethylation of dimethylsulfoniopropionate in cell extracts of sulfate-reducing bacteria. Arch. Microbiol. 169 (1998) 84–87. [PMID: 9396840]
2.  Reisch, C.R., Moran, M.A. and Whitman, W.B. Dimethylsulfoniopropionate-dependent demethylase (DmdA) from Pelagibacter ubique and Silicibacter pomeroyi. J. Bacteriol. 190 (2008) 8018–8024. [PMID: 18849431]
3.  Schuller, D.J., Reisch, C.R., Moran, M.A., Whitman, W.B. and Lanzilotta, W.N. Structures of dimethylsulfoniopropionate-dependent demethylase from the marine organism Pelagibacter ubique. Protein Sci. 21 (2012) 289–298. [PMID: 22162093]
[EC 2.1.1.269 created 2013]
 
 
EC 2.1.1.270     
Accepted name: (+)-6a-hydroxymaackiain 3-O-methyltransferase
Reaction: S-adenosyl-L-methionine + (+)-6a-hydroxymaackiain = S-adenosyl-L-homocysteine + (+)-pisatin
Glossary: (+)-6a-hydroxymaackiain = (6aR,12aR)-6H-[1,3]dioxolo[5,6][1]benzofuro[3,2-c]chromene-3,6a(12aH)-diol
(+)-pisatin = (6aR,12aR)-3-methoxy-6H-[1,3]dioxolo[5,6][1]benzofuro[3,2-c]chromen-6a(12aH)-ol
Other name(s): HM3OMT; HMM2
Systematic name: S-adenosyl-L-methionine:(+)-6a-hydroxymaackiain 3-O-methyltransferase
Comments: The protein from the plant Pisum sativum (garden pea) methylates (+)-6a-hydroxymaackiain at the 3-position. It also methylates 2,7,4′-trihydroxyisoflavanone on the 4′-position (cf. EC 2.1.1.212, 2,7,4-trihydroxyisoflavanone 4-O-methyltransferase) with lower activity.
References:
1.  Preisig, C.L., Matthews, D.E. and Vanetten, H.D. Purification and characterization of S-adenosyl-L-methionine:6a-hydroxymaackiain 3-O-methyltransferase from Pisum sativum. Plant Physiol. 91 (1989) 559–566. [PMID: 16667069]
2.  Wu, Q., Preisig, C.L. and VanEtten, H.D. Isolation of the cDNAs encoding (+)6a-hydroxymaackiain 3-O-methyltransferase, the terminal step for the synthesis of the phytoalexin pisatin in Pisum sativum. Plant Mol. Biol. 35 (1997) 551–560. [PMID: 9349277]
3.  Liu, C.J., Deavours, B.E., Richard, S.B., Ferrer, J.L., Blount, J.W., Huhman, D., Dixon, R.A. and Noel, J.P. Structural basis for dual functionality of isoflavonoid O-methyltransferases in the evolution of plant defense responses. Plant Cell 18 (2006) 3656–3669. [PMID: 17172354]
4.  Akashi, T., VanEtten, H.D., Sawada, Y., Wasmann, C.C., Uchiyama, H. and Ayabe, S. Catalytic specificity of pea O-methyltransferases suggests gene duplication for (+)-pisatin biosynthesis. Phytochemistry 67 (2006) 2525–2530. [PMID: 17067644]
[EC 2.1.1.270 created 2013]
 
 
EC 2.1.1.271     
Accepted name: cobalt-precorrin-4 methyltransferase
Reaction: S-adenosyl-L-methionine + cobalt-precorrin-4 = S-adenosyl-L-homocysteine + cobalt-precorrin-5A
Other name(s): CbiF
Systematic name: S-adenosyl-L-methionine:cobalt-precorrin-4 11-methyltransferase
Comments: Part of the anaerobic route to adenosylcobalamin.
References:
1.  Raux, E., Schubert, H.L., Woodcock, S.C., Wilson, K.S. and Warren, M.J. Cobalamin (vitamin B12) biosynthesis--cloning, expression and crystallisation of the Bacillus megaterium S-adenosyl-L-methionine-dependent cobalt-precorrin-4 transmethylase CbiF. Eur. J. Biochem. 254 (1998) 341–346. [PMID: 9660189]
2.  Schubert, H.L., Wilson, K.S., Raux, E., Woodcock, S.C. and Warren, M.J. The X-ray structure of a cobalamin biosynthetic enzyme, cobalt-precorrin-4 methyltransferase. Nat. Struct. Biol. 5 (1998) 585–592. [PMID: 9665173]
3.  Kajiwara, Y., Santander, P.J., Roessner, C.A., Perez, L.M. and Scott, A.I. Genetically engineered synthesis and structural characterization of cobalt-precorrin 5A and -5B, two new intermediates on the anaerobic pathway to vitamin B12: definition of the roles of the CbiF and CbiG enzymes. J. Am. Chem. Soc. 128 (2006) 9971–9978. [PMID: 16866557]
[EC 2.1.1.271 created 2013]
 
 
EC 2.1.1.272     
Accepted name: cobalt-factor III methyltransferase
Reaction: S-adenosyl-L-methionine + cobalt-factor III + reduced acceptor = S-adenosyl-L-homocysteine + cobalt-precorrin-4 + acceptor
Other name(s): CbiH60 (gene name)
Systematic name: S-adenosyl-L-methionine:cobalt-factor III 17-methyltransferase (ring contracting)
Comments: Isolated from Bacillus megaterium. The enzyme catalyses both methylation at C-17 and ring contraction. Contains a [4Fe-4S] cluster. It can also convert cobalt-precorrin-3 to cobalt-precorrin-4. The reductant may be thioredoxin.
References:
1.  Moore, S.J., Biedendieck, R., Lawrence, A.D., Deery, E., Howard, M.J., Rigby, S.E. and Warren, M.J. Characterization of the enzyme CbiH60 involved in anaerobic ring contraction of the cobalamin (vitamin B12) biosynthetic pathway. J. Biol. Chem. 288 (2013) 297–305. [PMID: 23155054]
[EC 2.1.1.272 created 2013]
 
 
EC 2.1.1.273     
Accepted name: benzoate O-methyltransferase
Reaction: S-adenosyl-L-methionine + benzoate = S-adenosyl-L-homocysteine + methyl benzoate
Other name(s): BAMT; S-adenosyl-L-methionine:benzoic acid carboxyl methyltransferase
Systematic name: S-adenosyl-L-methionine:benzoate O-methyltransferase
Comments: While the enzyme from the plant Zea mays is specific for benzoate [6], the enzymes from Arabidopsis species and Clarkia breweri also catalyse the reaction of EC 2.1.1.274, salicylate 1-O-methyltransferase [1,5]. In snapdragon (Antirrhinum majus) two isoforms are found, one specific for benzoate [2,3] and one that is also active towards salicylate [4]. The volatile product is an important scent compound in some flowering species [2].
References:
1.  Ross, J.R., Nam, K.H., D'Auria, J.C. and Pichersky, E. S-adenosyl-L-methionine:salicylic acid carboxyl methyltransferase, an enzyme involved in floral scent production and plant defense, represents a new class of plant methyltransferases. Arch. Biochem. Biophys. 367 (1999) 9–16. [PMID: 10375393]
2.  Dudareva, N., Murfitt, L.M., Mann, C.J., Gorenstein, N., Kolosova, N., Kish, C.M., Bonham, C. and Wood, K. Developmental regulation of methyl benzoate biosynthesis and emission in snapdragon flowers. Plant Cell 12 (2000) 949–961. [PMID: 10852939]
3.  Murfitt, L.M., Kolosova, N., Mann, C.J. and Dudareva, N. Purification and characterization of S-adenosyl-L-methionine:benzoic acid carboxyl methyltransferase, the enzyme responsible for biosynthesis of the volatile ester methyl benzoate in flowers of Antirrhinum majus. Arch. Biochem. Biophys. 382 (2000) 145–151. [PMID: 11051108]
4.  Negre, F., Kolosova, N., Knoll, J., Kish, C.M. and Dudareva, N. Novel S-adenosyl-L-methionine:salicylic acid carboxyl methyltransferase, an enzyme responsible for biosynthesis of methyl salicylate and methyl benzoate, is not involved in floral scent production in snapdragon flowers. Arch. Biochem. Biophys. 406 (2002) 261–270. [PMID: 12361714]
5.  Chen, F., D'Auria, J.C., Tholl, D., Ross, J.R., Gershenzon, J., Noel, J.P. and Pichersky, E. An Arabidopsis thaliana gene for methylsalicylate biosynthesis, identified by a biochemical genomics approach, has a role in defense. Plant J. 36 (2003) 577–588. [PMID: 14617060]
6.  Köllner, T.G., Lenk, C., Zhao, N., Seidl-Adams, I., Gershenzon, J., Chen, F. and Degenhardt, J. Herbivore-induced SABATH methyltransferases of maize that methylate anthranilic acid using s-adenosyl-L-methionine. Plant Physiol. 153 (2010) 1795–1807. [PMID: 20519632]
[EC 2.1.1.273 created 2013]
 
 
EC 2.1.1.274     
Accepted name: salicylate 1-O-methyltransferase
Reaction: S-adenosyl-L-methionine + salicylate = S-adenosyl-L-homocysteine + methyl salicylate
Glossary: methyl salicylate = methyl 2-hydroxybenzoate
Other name(s): SAMT; S-adenosyl-L-methionine:salicylic acid carboxyl methyltransferase; salicylate carboxymethyltransferase
Systematic name: S-adenosyl-L-methionine:salicylate 1-O-methyltransferase
Comments: The enzyme, which is found in flowering plants, also has the activity of EC 2.1.1.273, benzoate O-methyltransferase.
References:
1.  Ross, J.R., Nam, K.H., D'Auria, J.C. and Pichersky, E. S-adenosyl-L-methionine:salicylic acid carboxyl methyltransferase, an enzyme involved in floral scent production and plant defense, represents a new class of plant methyltransferases. Arch. Biochem. Biophys. 367 (1999) 9–16. [PMID: 10375393]
2.  Negre, F., Kolosova, N., Knoll, J., Kish, C.M. and Dudareva, N. Novel S-adenosyl-L-methionine:salicylic acid carboxyl methyltransferase, an enzyme responsible for biosynthesis of methyl salicylate and methyl benzoate, is not involved in floral scent production in snapdragon flowers. Arch. Biochem. Biophys. 406 (2002) 261–270. [PMID: 12361714]
3.  Chen, F., D'Auria, J.C., Tholl, D., Ross, J.R., Gershenzon, J., Noel, J.P. and Pichersky, E. An Arabidopsis thaliana gene for methylsalicylate biosynthesis, identified by a biochemical genomics approach, has a role in defense. Plant J. 36 (2003) 577–588. [PMID: 14617060]
4.  Zubieta, C., Ross, J.R., Koscheski, P., Yang, Y., Pichersky, E. and Noel, J.P. Structural basis for substrate recognition in the salicylic acid carboxyl methyltransferase family. Plant Cell 15 (2003) 1704–1716. [PMID: 12897246]
[EC 2.1.1.274 created 2013]
 
 
EC 2.1.1.275     
Accepted name: gibberellin A9 O-methyltransferase
Reaction: S-adenosyl-L-methionine + gibberellin A9 = S-adenosyl-L-homocysteine + methyl gibberellin A9
Glossary: gibberellin A9 = (1R,4aR,4bR,7R,9aR,10S,10aR)-1-methyl-8-methylene-13-oxododecahydro-4a,1-(epoxymethano)-7,9a-methanobenzo[a]azulene-10-carboxylic acid
methyl gibberellin A9 = methyl (1R,4aR,4bR,7R,9aR,10S,10aR)-1-methyl-8-methylene-13-oxododecahydro-4a,1-(epoxymethano)-7,9a-methanobenzo[a]azulene-10-carboxylate
Other name(s): GAMT1
Systematic name: S-adenosyl-L-methionine:gibberellin A9 O-methyltransferase
Comments: The enzyme also methylates gibberellins A20 (95%), A3 (80%), A4 (69%) and A34 (46%) with significant activity.
References:
1.  Varbanova, M., Yamaguchi, S., Yang, Y., McKelvey, K., Hanada, A., Borochov, R., Yu, F., Jikumaru, Y., Ross, J., Cortes, D., Ma, C.J., Noel, J.P., Mander, L., Shulaev, V., Kamiya, Y., Rodermel, S., Weiss, D. and Pichersky, E. Methylation of gibberellins by Arabidopsis GAMT1 and GAMT2. Plant Cell 19 (2007) 32–45. [PMID: 17220201]
[EC 2.1.1.275 created 2013]
 
 
EC 2.1.1.276     
Accepted name: gibberellin A4 carboxyl methyltransferase
Reaction: S-adenosyl-L-methionine + gibberellin A4 = S-adenosyl-L-homocysteine + methyl gibberellin A4
Glossary: gibberellin A4 = (1S,2S,4aR,4bR,7R,9aR,10S,10aR)-2-hydroxy-1-methyl-8-methylidene-13-oxododecahydro-4a,1-(epoxymethano)-7,9a-methanobenzo[a]azulene-10-carboxylic acid
methyl gibberellin A4 = methyl (1S,2S,4aR,4bR,7R,9aR,10S,10aR)-2-hydroxy-1-methyl-8-methylene-13-oxododecahydro-4a,1-(epoxymethano)-7,9a-methanobenzo[a]azulene-10-carboxylate
Other name(s): GAMT2; gibberellin A4 O-methyltransferase
Systematic name: S-adenosyl-L-methionine:gibberellin A4 O-methyltransferase
Comments: The enzyme also methylates gibberellins A34 (80%), A9 (60%), and A3 (45%) with significant activity.
References:
1.  Varbanova, M., Yamaguchi, S., Yang, Y., McKelvey, K., Hanada, A., Borochov, R., Yu, F., Jikumaru, Y., Ross, J., Cortes, D., Ma, C.J., Noel, J.P., Mander, L., Shulaev, V., Kamiya, Y., Rodermel, S., Weiss, D. and Pichersky, E. Methylation of gibberellins by Arabidopsis GAMT1 and GAMT2. Plant Cell 19 (2007) 32–45. [PMID: 17220201]
[EC 2.1.1.276 created 2013]
 
 
EC 2.1.1.277     
Accepted name: anthranilate O-methyltransferase
Reaction: S-adenosyl-L-methionine + anthranilate = S-adenosyl-L-homocysteine + O-methyl anthranilate
Other name(s): AAMT
Systematic name: S-adenosyl-L-methionine:anthranilate O-methyltransferase
Comments: In the plant maize (Zea mays), the isoforms AAMT1 and AAMT2 are specific for anthranilate while AAMT3 also has the activity of EC 2.1.1.273, benzoate methyltransferase.
References:
1.  Köllner, T.G., Lenk, C., Zhao, N., Seidl-Adams, I., Gershenzon, J., Chen, F. and Degenhardt, J. Herbivore-induced SABATH methyltransferases of maize that methylate anthranilic acid using s-adenosyl-L-methionine. Plant Physiol. 153 (2010) 1795–1807. [PMID: 20519632]
[EC 2.1.1.277 created 2013]
 
 
EC 2.1.1.278     
Accepted name: indole-3-acetate O-methyltransferase
Reaction: S-adenosyl-L-methionine + (indol-3-yl)acetate = S-adenosyl-L-homocysteine + methyl (indol-3-yl)acetate
Other name(s): IAA carboxylmethyltransferase; IAMT
Systematic name: S-adenosyl-L-methionine:(indol-3-yl)acetate O-methyltransferase
Comments: Binds Mg2+. The enzyme is found in plants and is important for regulation of the plant hormone (indol-3-yl)acetate. The product, methyl (indol-3-yl)acetate is inactive as hormone [2].
References:
1.  Zubieta, C., Ross, J.R., Koscheski, P., Yang, Y., Pichersky, E. and Noel, J.P. Structural basis for substrate recognition in the salicylic acid carboxyl methyltransferase family. Plant Cell 15 (2003) 1704–1716. [PMID: 12897246]
2.  Li, L., Hou, X., Tsuge, T., Ding, M., Aoyama, T., Oka, A., Gu, H., Zhao, Y. and Qu, L.J. The possible action mechanisms of indole-3-acetic acid methyl ester in Arabidopsis. Plant Cell Rep. 27 (2008) 575–584. [PMID: 17926040]
3.  Zhao, N., Ferrer, J.L., Ross, J., Guan, J., Yang, Y., Pichersky, E., Noel, J.P. and Chen, F. Structural, biochemical, and phylogenetic analyses suggest that indole-3-acetic acid methyltransferase is an evolutionarily ancient member of the SABATH family. Plant Physiol. 146 (2008) 455–467. [PMID: 18162595]
[EC 2.1.1.278 created 2013]
 
 
EC 2.1.1.279     
Accepted name: trans-anol O-methyltransferase
Reaction: (1) S-adenosyl-L-methionine + trans-anol = S-adenosyl-L-homocysteine + trans-anethole
(2) S-adenosyl-L-methionine + isoeugenol = S-adenosyl-L-homocysteine + isomethyleugenol
Glossary: trans-anol = 4-[(1E)-prop-1-en-1-yl]phenol
trans-anethole = 1-methoxy-4-[(1E)-prop-1-en-1-yl]benzene
Other name(s): AIMT1; S-adenosyl-L-methionine:t-anol/isoeugenol O-methyltransferase; t-anol O-methyltransferase
Systematic name: S-adenosyl-L-methionine:trans-anol O-methyltransferase
Comments: The enzyme from anise (Pimpinella anisum) is highly specific for substrates in which the double bond in the propenyl side chain is located between C7 and C8, and, in contrast to EC 2.1.1.146, (iso)eugenol O-methyltransferase, does not have activity with eugenol or chavicol.
References:
1.  Koeduka, T., Baiga, T.J., Noel, J.P. and Pichersky, E. Biosynthesis of t-anethole in anise: characterization of t-anol/isoeugenol synthase and an O-methyltransferase specific for a C7-C8 propenyl side chain. Plant Physiol. 149 (2009) 384–394. [PMID: 18987218]
[EC 2.1.1.279 created 2013]
 
 
EC 2.1.1.280     
Accepted name: selenocysteine Se-methyltransferase
Reaction: S-methyl-L-methionine + L-selenocysteine = L-methionine + Se-methyl-L-selenocysteine
Other name(s): SMT
Systematic name: S-methyl-L-methionine:L-selenocysteine Se-methyltransferase
Comments: The enzyme uses S-adenosyl-L-methionine as methyl donor less actively than S-methyl-L-methionine. The enzyme from broccoli (Brassica oleracea var. italica) also has the activity of EC 2.1.1.10, homocysteine S-methyltransferase [4].
References:
1.  Neuhierl, B. and Bock, A. On the mechanism of selenium tolerance in selenium-accumulating plants. Purification and characterization of a specific selenocysteine methyltransferase from cultured cells of Astragalus bisculatus. Eur. J. Biochem. 239 (1996) 235–238. [PMID: 8706715]
2.  Neuhierl, B., Thanbichler, M., Lottspeich, F. and Bock, A. A family of S-methylmethionine-dependent thiol/selenol methyltransferases. Role in selenium tolerance and evolutionary relation. J. Biol. Chem. 274 (1999) 5407–5414. [PMID: 10026151]
3.  Lyi, S.M., Heller, L.I., Rutzke, M., Welch, R.M., Kochian, L.V. and Li, L. Molecular and biochemical characterization of the selenocysteine Se-methyltransferase gene and Se-methylselenocysteine synthesis in broccoli. Plant Physiol. 138 (2005) 409–420. [PMID: 15863700]
4.  Lyi, S.M., Zhou, X., Kochian, L.V. and Li, L. Biochemical and molecular characterization of the homocysteine S-methyltransferase from broccoli (Brassica oleracea var. italica). Phytochemistry 68 (2007) 1112–1119. [PMID: 17391716]
[EC 2.1.1.280 created 2013]
 
 
EC 2.1.1.281     
Accepted name: phenylpyruvate C3-methyltransferase
Reaction: S-adenosyl-L-methionine + 3-phenylpyruvate = S-adenosyl-L-homocysteine + (3S)-2-oxo-3-phenylbutanoate
Glossary: 3-phenylpyruvate = 2-oxo-3-phenylpropanoate
(3S)-2-oxo-3-phenylbutanoate = (3S)-β-methyl-phenylpyruvate
Other name(s): phenylpyruvate Cβ-methyltransferase; phenylpyruvate methyltransferase; mppJ (gene name)
Systematic name: S-adenosyl-L-methionine:2-oxo-3-phenylpropanoate C3-methyltransferase
Comments: The enzyme from the bacterium Streptomyces hygroscopicus NRRL3085 is involved in synthesis of the nonproteinogenic amino acid (2S,3S)-β-methyl-phenylalanine, a building block of the antibiotic mannopeptimycin.
References:
1.  Huang, Y.T., Lyu, S.Y., Chuang, P.H., Hsu, N.S., Li, Y.S., Chan, H.C., Huang, C.J., Liu, Y.C., Wu, C.J., Yang, W.B. and Li, T.L. In vitro characterization of enzymes involved in the synthesis of nonproteinogenic residue (2S,3S)-β-methylphenylalanine in glycopeptide antibiotic mannopeptimycin. ChemBioChem 10 (2009) 2480–2487. [PMID: 19731276]
[EC 2.1.1.281 created 2013]
 
 
EC 2.1.1.282     
Accepted name: tRNAPhe 7-[(3-amino-3-carboxypropyl)-4-demethylwyosine37-N4]-methyltransferase
Reaction: S-adenosyl-L-methionine + 7-[(3S)-(3-amino-3-carboxypropyl)]-4-demethylwyosine37 in tRNAPhe = S-adenosyl-L-homocysteine + 7-[(3S)-(3-amino-3-carboxypropyl)]wyosine37 in tRNAPhe
Glossary: wyosine = 4,6-dimethyl-3-(β-D-ribofuranosyl)-3,4-dihydro-9H-imidazo[1,2-a]purin-9-one
wybutosine = yW = 7-{(3S)-4-methoxy-3-[(methoxycarbonyl)amino]-4-oxobutyl}-4,5-dimethyl-3-(β-D-ribofuranosyl)-3,4-dihydro-9H-imidazo[1,2-a]purin-9-one
Other name(s): TYW3 (gene name); tRNA-yW synthesizing enzyme-3
Systematic name: S-adenosyl-L-methionine:tRNAPhe 7-[(3S)-(3-amino-3-carboxypropyl)-4-demethylwyosine-N4]-methyltransferase
Comments: The enzyme is involved in the biosynthesis of hypermodified tricyclic bases found at position 37 of certain tRNAs. These modifications are important for translational reading-frame maintenance. The enzyme is found in all eukaryotes and in some archaea, but not in bacteria. The eukaryotic enzyme is involved in the biosynthesis of wybutosine.
References:
1.  Noma, A., Kirino, Y., Ikeuchi, Y. and Suzuki, T. Biosynthesis of wybutosine, a hyper-modified nucleoside in eukaryotic phenylalanine tRNA. EMBO J. 25 (2006) 2142–2154. [PMID: 16642040]
[EC 2.1.1.282 created 2013, modified 2014]
 
 
EC 2.1.1.283     
Accepted name: emodin O-methyltransferase
Reaction: S-adenosyl-L-methionine + emodin = S-adenosyl-L-homocysteine + questin
Glossary: emodin = 1,3,8-trihydroxy-6-methyl-9,10-anthraquinone
questin = 1,6-dihydroxy-8-methoxy-3-methyl-9,10-anthraquinone
Other name(s): EOMT
Systematic name: S-adenosyl-L-methionine:emodin 8-O-methyltransferase
Comments: The enzyme is involved in biosynthesis of the seco-anthraquinone (+)-geodin.
References:
1.  Chen, Z.G., Fujii, I., Ebizuka, Y. and Sankawa, U. Emodin O-methyltransferase from Aspergillus terreus. Arch. Microbiol. 158 (1992) 29–34. [PMID: 1444712]
[EC 2.1.1.283 created 2013]
 
 
EC 2.1.1.284     
Accepted name: 8-demethylnovobiocic acid C8-methyltransferase
Reaction: S-adenosyl-L-methionine + 8-demethylnovobiocic acid = S-adenosyl-L-homocysteine + novobiocic acid
Glossary: novobiocic acid = N-(2,7-dihydroxy-8-methyl-4-oxochromen-3-yl)-4-hydroxy-3-(3-methylbut-2-enyl) benzamide
Other name(s): NovO
Systematic name: S-adenosyl-L-methionine:8-demethylnovobiocic acid C8-methyltransferase
Comments: The enzyme is involved in the biosynthesis of the aminocoumarin antibiotic novobiocin.
References:
1.  Pacholec, M., Tao, J. and Walsh, C.T. CouO and NovO: C-methyltransferases for tailoring the aminocoumarin scaffold in coumermycin and novobiocin antibiotic biosynthesis. Biochemistry 44 (2005) 14969–14976. [PMID: 16274243]
[EC 2.1.1.284 created 2013]
 
 
EC 2.1.1.285     
Accepted name: demethyldecarbamoylnovobiocin O-methyltransferase
Reaction: S-adenosyl-L-methionine + demethyldecarbamoylnovobiocin = S-adenosyl-L-homocysteine + decarbamoylnovobiocin
Glossary: demethyldecarbamoylnovobiocin = N-{7-[(6-deoxy-5-methyl-β-D-gulopyranosyl)oxy]-4-hydroxy-8-methyl-2-oxo-2H-chromen-3-yl}-4-hydroxy-3-(3-methylbut-2-en-1-yl)benzamide
decarbamoylnovobiocin = N-{7-[(6-deoxy-5-methyl-4-O-methyl-β-D-gulopyranosyl)oxy]4-hydroxy-8-methyl-2-oxo-2H-chromen-3-yl}-4-hydroxy-3-(3-methyl-2-buten-1-yl)benzamide
Other name(s): NovP
Systematic name: S-adenosyl-L-methionine:demethyldecarbamoylnovobiocin 4′′-O-methyltransferase
Comments: The enzyme is involved in the biosynthesis of the aminocoumarin antibiotic novobiocin.
References:
1.  Freel Meyers, C.L., Oberthur, M., Xu, H., Heide, L., Kahne, D. and Walsh, C.T. Characterization of NovP and NovN: completion of novobiocin biosynthesis by sequential tailoring of the noviosyl ring. Angew. Chem. Int. Ed. Engl. 43 (2004) 67–70. [PMID: 14694473]
2.  Gomez Garcia, I., Stevenson, C.E., Uson, I., Freel Meyers, C.L., Walsh, C.T. and Lawson, D.M. The crystal structure of the novobiocin biosynthetic enzyme NovP: the first representative structure for the TylF O-methyltransferase superfamily. J. Mol. Biol. 395 (2010) 390–407. [PMID: 19857499]
[EC 2.1.1.285 created 2013]
 
 
EC 2.1.1.286     
Accepted name: 25S rRNA (adenine2142-N1)-methyltransferase
Reaction: S-adenosyl-L-methionine + adenine2142 in 25S rRNA = S-adenosyl-L-homocysteine + N1-methyladenine2142 in 25S rRNA
Other name(s): BMT2 (gene name); 25S rRNA m1A2142 methyltransferase
Systematic name: S-adenosyl-L-methionine:25S rRNA (adenine2142-N1)-methyltransferase
Comments: In the yeast Saccharomyces cerevisiae this methylation is important for resistance towards hydrogen peroxide and the antibiotic anisomycin.
References:
1.  Sharma, S., Watzinger, P., Kotter, P. and Entian, K.D. Identification of a novel methyltransferase, Bmt2, responsible for the N-1-methyl-adenosine base modification of 25S rRNA in Saccharomyces cerevisiae. Nucleic Acids Res. 41 (2013) 5428–5443. [PMID: 23558746]
[EC 2.1.1.286 created 2013]
 
 
EC 2.1.1.287     
Accepted name: 25S rRNA (adenine645-N1)-methyltransferase
Reaction: S-adenosyl-L-methionine + adenine645 in 25S rRNA = S-adenosyl-L-homocysteine + N1-methyladenine645 in 25S rRNA
Other name(s): 25S rRNA m1A645 methyltransferase; Rrp8
Systematic name: S-adenosyl-L-methionine:25S rRNA (adenine645-N1)-methyltransferase
Comments: The enzyme is found in eukaryotes. The adenine position refers to rRNA in the yeast Saccharomyces cerevisiae, in which the enzyme is important for ribosome biogenesis.
References:
1.  Peifer, C., Sharma, S., Watzinger, P., Lamberth, S., Kotter, P. and Entian, K.D. Yeast Rrp8p, a novel methyltransferase responsible for m1A 645 base modification of 25S rRNA. Nucleic Acids Res. 41 (2013) 1151–1163. [PMID: 23180764]
[EC 2.1.1.287 created 2013]
 
 
EC 2.1.1.288     
Accepted name: aklanonic acid methyltransferase
Reaction: S-adenosyl-L-methionine + aklanonate = S-adenosyl-L-homocysteine + methyl aklanonate
Glossary: methyl aklanonate = methyl [1,4,5-trihydroxy-9,10-dioxo-3-(3-oxopentanoyl)-9,10-dihydroanthracen-2-yl]acetate
aklanonate = [4,5-dihydroxy-9,10-dioxo-3-(3-oxopentanoyl)-9,10-dihydroanthracen-2-yl]acetic acid
Other name(s): DauC; AAMT
Systematic name: S-adenosyl-L-methionine:aklanonate O-methyltransferase
Comments: The enzyme from the Gram-positive bacterium Streptomyces sp. C5 is involved in the biosynthesis of the anthracycline daunorubicin.
References:
1.  Dickens, M.L., Ye, J. and Strohl, W.R. Analysis of clustered genes encoding both early and late steps in daunomycin biosynthesis by Streptomyces sp. strain C5. J. Bacteriol. 177 (1995) 536–543. [PMID: 7836284]
[EC 2.1.1.288 created 2013]
 
 
EC 2.1.1.289     
Accepted name: cobalt-precorrin-7 (C5)-methyltransferase
Reaction: cobalt-precorrin-7 + S-adenosyl-L-methionine = cobalt-precorrin-8 + S-adenosyl-L-homocysteine
Other name(s): CbiE
Systematic name: S-adenosyl-L-methionine:precorrin-7 C5-methyltransferase
Comments: This enzyme catalyses the methylation at C-5 of cobalt-precorrin-7, a step in the anaerobic (early cobalt insertion) adenosylcobalamin biosynthesis pathway.
References:
1.  Santander, P.J., Kajiwara, Y., Williams, H.J. and Scott, A.I. Structural characterization of novel cobalt corrinoids synthesized by enzymes of the vitamin B12 anaerobic pathway. Bioorg. Med. Chem. 14 (2006) 724–731. [PMID: 16198574]
2.  Moore, S.J., Lawrence, A.D., Biedendieck, R., Deery, E., Frank, S., Howard, M.J., Rigby, S.E. and Warren, M.J. Elucidation of the anaerobic pathway for the corrin component of cobalamin (vitamin B12). Proc. Natl. Acad. Sci. USA 110 (2013) 14906–14911. [PMID: 23922391]
[EC 2.1.1.289 created 2010]
 
 
EC 2.1.1.290     
Accepted name: tRNAPhe [7-(3-amino-3-carboxypropyl)wyosine37-O]-methyltransferase
Reaction: S-adenosyl-L-methionine + 7-[(3S)-3-amino-3-carboxypropyl]wyosine37 in tRNAPhe = S-adenosyl-L-homocysteine + 7-[(3S)-3-amino-3-(methoxycarbonyl)propyl]wyosine37 in tRNAPhe
Glossary: wyosine = 4,6-dimethyl-3-(β-D-ribofuranosyl)-3,4-dihydro-9H-imidazo[1,2-a]purin-9-one
wybutosine = yW = 7-[(3S)-3-(methoxycarbonyl)-3-(methoxycarbonylamino)propyl]-4,5-dimethyl-3-(β-D-ribofuranosyl)-3,4-dihydro-9H-imidazo[1,2-a]purin-9-one
Other name(s): TYW4 (ambiguous); tRNA-yW synthesizing enzyme-4 (ambiguous)
Systematic name: S-adenosyl-L-methionine:tRNAPhe {7-[(3S)-3-amino-3-carboxypropyl]wyosine37-O}-methyltransferase
Comments: The enzyme is found only in eukaryotes, where it is involved in the biosynthesis of wybutosine, a hypermodified tricyclic base found at position 37 of certain tRNAs. The modification is important for translational reading-frame maintenance. In some species that produce hydroxywybutosine the enzyme uses 7-(2-hydroxy-3-amino-3-carboxypropyl)wyosine37 in tRNAPhe as substrate. The enzyme also has the activity of EC 2.3.1.231, tRNAPhe 7-[(3S)-4-methoxy-(3-amino-3-carboxypropyl)wyosine37-O]-carbonyltransferase [2].
References:
1.  Noma, A., Kirino, Y., Ikeuchi, Y. and Suzuki, T. Biosynthesis of wybutosine, a hyper-modified nucleoside in eukaryotic phenylalanine tRNA. EMBO J. 25 (2006) 2142–2154. [PMID: 16642040]
2.  Suzuki, Y., Noma, A., Suzuki, T., Ishitani, R. and Nureki, O. Structural basis of tRNA modification with CO2 fixation and methylation by wybutosine synthesizing enzyme TYW4. Nucleic Acids Res. 37 (2009) 2910–2925. [PMID: 19287006]
3.  Kato, M., Araiso, Y., Noma, A., Nagao, A., Suzuki, T., Ishitani, R. and Nureki, O. Crystal structure of a novel JmjC-domain-containing protein, TYW5, involved in tRNA modification. Nucleic Acids Res. 39 (2011) 1576–1585. [PMID: 20972222]
[EC 2.1.1.290 created 2013]
 
 
EC 2.1.1.291     
Accepted name: (R,S)-reticuline 7-O-methyltransferase
Reaction: (1) S-adenosyl-L-methionine + (S)-reticuline = S-adenosyl-L-homocysteine + (S)-laudanine
(2) S-adenosyl-L-methionine + (R)-reticuline = S-adenosyl-L-homocysteine + (R)-laudanine
Glossary: (S)-reticuline = (1S)-1-[(3-hydroxy-4-methoxyphenyl)methyl]-6-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ol
(R)-reticuline = (1R)-1-[(3-hydroxy-4-methoxyphenyl)methyl]-6-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ol
(S)-laudanine = 5-[((1S)-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinolin-1-yl)methyl]-2-methoxyphenol
(R)-laudanine = 5-[((1R)-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinolin-1-yl)methyl]-2-methoxyphenol
Systematic name: S-adenosyl-L-methionine:(R,S)-reticuline 7-O-methyltransferase
Comments: The enzyme from the plant Papaver somniferum (opium poppy) methylates (S)- and (R)-reticuline with equal efficiency and is involved in the biosynthesis of tetrahydrobenzylisoquinoline alkaloids.
References:
1.  Ounaroon, A., Decker, G., Schmidt, J., Lottspeich, F. and Kutchan, T.M. (R,S)-Reticuline 7-O-methyltransferase and (R,S)-norcoclaurine 6-O-methyltransferase of Papaver somniferum - cDNA cloning and characterization of methyl transfer enzymes of alkaloid biosynthesis in opium poppy. Plant J. 36 (2003) 808–819. [PMID: 14675446]
2.  Weid, M., Ziegler, J. and Kutchan, T.M. The roles of latex and the vascular bundle in morphine biosynthesis in the opium poppy, Papaver somniferum. Proc. Natl. Acad. Sci. USA 101 (2004) 13957–13962. [PMID: 15353584]
[EC 2.1.1.291 created 2013]
 
 
EC 2.1.1.292     
Accepted name: carminomycin 4-O-methyltransferase
Reaction: S-adenosyl-L-methionine + carminomycin = S-adenosyl-L-homocysteine + daunorubicin
Glossary: daunorubicin = (+)-daunomycin = (8S,10S)-8-acetyl-10-[(2S,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,8,11-trihydroxy-1-methoxy-9,10-dihydro-7H-tetracene-5,12-dione
carminomycin = (1S,3S)-3-acetyl-3,5,10,12-tetrahydroxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranoside = (1S,3S)-3-acetyl-3,5,10,12-tetrahydroxy-6,11-dioxo-1,2,3,4,6,11-hexahydronaphthacen-1-yl 3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranoside
carubicin = (1S,3S)-3-acetyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranoside
= (8S,10S)-8-acetyl-10-[(3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)oxy]-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydronaphthacene-5,12-dione
Other name(s): DnrK; DauK
Systematic name: S-adenosyl-L-methionine:carminomycin 4-O-methyltransferase
Comments: The enzymes from the Gram-positive bacteria Streptomyces sp. C5 and Streptomyces peucetius are involved in the biosynthesis of the anthracycline daunorubicin. In vitro the enzyme from Streptomyces sp. C5 also catalyses the 4-O-methylation of 13-dihydrocarminomycin, rhodomycin D and 10-carboxy-13-deoxycarminomycin [3].
References:
1.  Connors, N.C. and Strohl, W.R. Partial purification and properties of carminomycin 4-O-methyltransferase from Streptomyces sp. strain C5. J. Gen. Microbiol. 139 Pt 6 (1993) 1353–1362. [PMID: 8360627]
2.  Jansson, A., Koskiniemi, H., Mantsala, P., Niemi, J. and Schneider, G. Crystal structure of a ternary complex of DnrK, a methyltransferase in daunorubicin biosynthesis, with bound products. J. Biol. Chem. 279 (2004) 41149–41156. [PMID: 15273252]
3.  Dickens, M.L., Priestley, N.D. and Strohl, W.R. In vivo and in vitro bioconversion of ε-rhodomycinone glycoside to doxorubicin: functions of DauP, DauK, and DoxA. J. Bacteriol. 179 (1997) 2641–2650. [PMID: 9098063]
[EC 2.1.1.292 created 2013]
 
 
EC 2.1.1.293     
Accepted name: 6-hydroxytryprostatin B O-methyltransferase
Reaction: S-adenosyl-L-methionine + 6-hydroxytryprostatin B = S-adenosyl-L-homocysteine + tryprostatin A
Glossary: 6-hydroxytryprostatin B = (3S,8aS)-3-{[6-hydroxy-2-(3-methylbut-2-en-1-yl)-1H-indol-3-yl]methyl}hexahydropyrrolo[1,2-a]pyrazine-1,4-dione
tryprostatin A = (3S,8aS)-3-{[6-methoxy-2-(3-methylbut-2-en-1-yl)-1H-indol-3-yl]methyl}hexahydropyrrolo[1,2-a]pyrazine-1,4-dione
Other name(s): ftmD (gene name)
Systematic name: S-adenosyl-L-methionine:6-hydroxytryprostatin B O-methyltransferase
Comments: Involved in the biosynthetic pathways of several indole alkaloids such as tryprostatins, fumitremorgins and verruculogen.
References:
1.  Kato, N., Suzuki, H., Okumura, H., Takahashi, S. and Osada, H. A point mutation in ftmD blocks the fumitremorgin biosynthetic pathway in Aspergillus fumigatus strain Af293. Biosci. Biotechnol. Biochem. 77 (2013) 1061–1067. [PMID: 23649274]
[EC 2.1.1.293 created 2013]
 
 
EC 2.1.1.294     
Accepted name: 3-O-phospho-polymannosyl GlcNAc-diphospho-ditrans,octacis-undecaprenol 3-phospho-methyltransferase
Reaction: S-adenosyl-L-methionine + 3-O-phospho-α-D-Man-(1→2)-α-D-Man-(1→2)-[α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-Man-(1→2)-α-D-Man-(1→2)]n-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-GlcNAc-diphospho-ditrans,octacis-undecaprenol = S-adenosyl-L-homocysteine + 3-O-methylphospho-α-D-Man-(1→2)-α-D-Man-(1→2)-[α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-Man-(1→2)-α-D-Man-(1→2)]n-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-GlcNAc-diphospho-ditrans,octacis-undecaprenol
Other name(s): WbdD; S-adenosyl-L-methionine:3-O-phospho-α-D-Man-(1→2)-α-D-Man-(1→2)-α-D-Man-(1→3)-α-D-Man-(1→3)-[α-D-Man-(1→2)-α-D-Man-(1→2)-α-D-Man-(1→3)-α-D-Man-(1→3)]n-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-GlcNAc-α-diphospho-ditrans,octacis-undecaprenol 3-phospho-methyltransferase
Systematic name: S-adenosyl-L-methionine:3-O-phospho-α-D-Man-(1→2)-α-D-Man-(1→2)-[α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-Man-(1→2)-α-D-Man-(1→2)]n-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-GlcNAc-diphospho-ditrans,octacis-undecaprenol 3-phospho-methyltransferase
Comments: The enzyme is involved in the biosynthesis of the polymannose O-polysaccharide in the outer leaflet of the membrane of Escherichia coli serotype O9a. O-Polysaccharide structures vary extensively because of differences in the number and type of sugars in the repeat unit. The dual kinase/methylase WbdD also catalyses the preceding phosphorylation of α-D-Man-(1→2)-α-D-Man-(1→2)-[α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-Man-(1→2)-α-D-Man-(1→2)]n-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-GlcNAc-diphospho-ditrans,octacis-undecaprenol (cf. EC 2.7.1.181, polymannosyl GlcNAc-diphospho-ditrans,octacis-undecaprenol kinase).
References:
1.  Clarke, B.R., Cuthbertson, L. and Whitfield, C. Nonreducing terminal modifications determine the chain length of polymannose O antigens of Escherichia coli and couple chain termination to polymer export via an ATP-binding cassette transporter. J. Biol. Chem. 279 (2004) 35709–35718. [PMID: 15184370]
2.  Clarke, B.R., Greenfield, L.K., Bouwman, C. and Whitfield, C. Coordination of polymerization, chain termination, and export in assembly of the Escherichia coli lipopolysaccharide O9a antigen in an ATP-binding cassette transporter-dependent pathway. J. Biol. Chem. 284 (2009) 30662–30672. [PMID: 19734145]
3.  Clarke, B.R., Richards, M.R., Greenfield, L.K., Hou, D., Lowary, T.L. and Whitfield, C. In vitro reconstruction of the chain termination reaction in biosynthesis of the Escherichia coli O9a O-polysaccharide: the chain-length regulator, WbdD, catalyzes the addition of methyl phosphate to the non-reducing terminus of the growing glycan. J. Biol. Chem. 286 (2011) 41391–41401. [PMID: 21990359]
4.  Liston, S.D., Clarke, B.R., Greenfield, L.K., Richards, M.R., Lowary, T.L. and Whitfield, C. Domain interactions control complex formation and polymerase specificity in the biosynthesis of the Escherichia coli O9a antigen. J. Biol. Chem. 290 (2015) 1075–1085. [PMID: 25422321]
[EC 2.1.1.294 created 2014, modified 2018]
 
 
EC 2.1.1.295     
Accepted name: 2-methyl-6-phytyl-1,4-hydroquinone methyltransferase
Reaction: (1) S-adenosyl-L-methionine + 2-methyl-6-phytylbenzene-1,4-diol = S-adenosyl-L-homocysteine + 2,3-dimethyl-6-phytylbenzene-1,4-diol
(2) S-adenosyl-L-methionine + 2-methyl-6-all-trans-nonaprenylbenzene-1,4-diol = S-adenosyl-L-homocysteine + plastoquinol
(3) S-adenosyl-L-methionine + 6-geranylgeranyl-2-methylbenzene-1,4-diol = S-adenosyl-L-homocysteine + 6-geranylgeranyl-2,3-dimethylbenzene-1,4-diol
Other name(s): VTE3 (gene name); 2-methyl-6-solanyl-1,4-hydroquinone methyltransferase; MPBQ/MSBQ methyltransferase; MPBQ/MSBQ MT
Systematic name: S-adenosyl-L-methionine:2-methyl-6-phytyl-1,4-benzoquinol C-3-methyltransferase
Comments: Involved in the biosynthesis of plastoquinol, as well as vitamin E (tocopherols and tocotrienols).
References:
1.  Shintani, D.K., Cheng, Z. and DellaPenna, D. The role of 2-methyl-6-phytylbenzoquinone methyltransferase in determining tocopherol composition in Synechocystis sp. PCC6803. FEBS Lett. 511 (2002) 1–5. [PMID: 11821038]
2.  Cheng, Z., Sattler, S., Maeda, H., Sakuragi, Y., Bryant, D.A. and DellaPenna, D. Highly divergent methyltransferases catalyze a conserved reaction in tocopherol and plastoquinone synthesis in cyanobacteria and photosynthetic eukaryotes. Plant Cell 15 (2003) 2343–2356. [PMID: 14508009]
3.  Van Eenennaam, A.L., Lincoln, K., Durrett, T.P., Valentin, H.E., Shewmaker, C.K., Thorne, G.M., Jiang, J., Baszis, S.R., Levering, C.K., Aasen, E.D., Hao, M., Stein, J.C., Norris, S.R. and Last, R.L. Engineering vitamin E content: from Arabidopsis mutant to soy oil. Plant Cell 15 (2003) 3007–3019. [PMID: 14630966]
[EC 2.1.1.295 created 2014]
 
 
EC 2.1.1.296     
Accepted name: methyltransferase cap2
Reaction: S-adenosyl-L-methionine + a 5′-(N7-methyl 5′-triphosphoguanosine)-(2′-O-methyl-purine-ribonucleotide)-(ribonucleotide)-[mRNA] = S-adenosyl-L-homocysteine + a 5′-(N7-methyl 5′-triphosphoguanosine)-(2′-O-methyl-purine-ribonucleotide)-(2′-O-methyl-ribonucleotide)-[mRNA]
Other name(s): MTR2; cap2-MTase; mRNA (nucleoside-2′-O)-methyltransferase (ambiguous)
Systematic name: S-adenosyl-L-methionine:5′-(N7-methyl 5′-triphosphoguanosine)-(2′-O-methyl-purine-ribonucleotide)-ribonucleotide-[mRNA] 2′-O-methyltransferase
Comments: The enzyme, found in higher eukaryotes including insects and vertebrates, and their viruses, methylates the ribose of the ribonucleotide at the second transcribed position of mRNAs and snRNAs. This methylation event is known as cap2. The human enzyme can also methylate mRNA molecules where the upstream purine ribonucleotide is not methylated (see EC 2.1.1.57, methyltransferase cap1), but with lower efficiency [2].
References:
1.  Arhin, G.K., Ullu, E. and Tschudi, C. 2′-O-methylation of position 2 of the trypanosome spliced leader cap 4 is mediated by a 48 kDa protein related to vaccinia virus VP39. Mol. Biochem. Parasitol. 147 (2006) 137–139. [PMID: 16516986]
2.  Werner, M., Purta, E., Kaminska, K.H., Cymerman, I.A., Campbell, D.A., Mittra, B., Zamudio, J.R., Sturm, N.R., Jaworski, J. and Bujnicki, J.M. 2′-O-ribose methylation of cap2 in human: function and evolution in a horizontally mobile family. Nucleic Acids Res. 39 (2011) 4756–4768. [PMID: 21310715]
[EC 2.1.1.296 created 2014]
 
 
EC 2.1.1.297     
Accepted name: peptide chain release factor N5-glutamine methyltransferase
Reaction: S-adenosyl-L-methionine + [peptide chain release factor 1 or 2]-L-glutamine = S-adenosyl-L-homocysteine + [peptide chain release factor 1 or 2]-N5-methyl-L-glutamine
Other name(s): N5-glutamine S-adenosyl-L-methionine dependent methyltransferase; N5-glutamine MTase; HemK; PrmC
Systematic name: S-adenosyl-L-methionine:[peptide chain release factor 1 or 2]-L-glutamine (N5-glutamine)-methyltransferase
Comments: Modifies the glutamine residue in the universally conserved glycylglycylglutamine (GGQ) motif of peptide chain release factor, resulting in almost complete loss of release activity.
References:
1.  Nakahigashi, K., Kubo, N., Narita, S., Shimaoka, T., Goto, S., Oshima, T., Mori, H., Maeda, M., Wada, C. and Inokuchi, H. HemK, a class of protein methyl transferase with similarity to DNA methyl transferases, methylates polypeptide chain release factors, and hemK knockout induces defects in translational termination. Proc. Natl. Acad. Sci. USA 99 (2002) 1473–1478. [PMID: 11805295]
2.  Heurgue-Hamard, V., Champ, S., Engstrom, A., Ehrenberg, M. and Buckingham, R.H. The hemK gene in Escherichia coli encodes the N5-glutamine methyltransferase that modifies peptide release factors. EMBO J. 21 (2002) 769–778. [PMID: 11847124]
3.  Schubert, H.L., Phillips, J.D. and Hill, C.P. Structures along the catalytic pathway of PrmC/HemK, an N5-glutamine AdoMet-dependent methyltransferase. Biochemistry 42 (2003) 5592–5599. [PMID: 12741815]
4.  Yoon, H.J., Kang, K.Y., Ahn, H.J., Shim, S.M., Ha, J.Y., Lee, S.K., Mikami, B. and Suh, S.W. X-ray crystallographic studies of HemK from Thermotoga maritima, an N5-glutamine methyltransferase. Mol. Cells 16 (2003) 266–269. [PMID: 14651272]
5.  Yang, Z., Shipman, L., Zhang, M., Anton, B.P., Roberts, R.J. and Cheng, X. Structural characterization and comparative phylogenetic analysis of Escherichia coli HemK, a protein (N5)-glutamine methyltransferase. J. Mol. Biol. 340 (2004) 695–706. [PMID: 15223314]
6.  Pannekoek, Y., Heurgue-Hamard, V., Langerak, A.A., Speijer, D., Buckingham, R.H. and van der Ende, A. The N5-glutamine S-adenosyl-L-methionine-dependent methyltransferase PrmC/HemK in Chlamydia trachomatis methylates class 1 release factors. J. Bacteriol. 187 (2005) 507–511. [PMID: 15629922]
[EC 2.1.1.297 created 2014]
 
 
EC 2.1.1.298     
Accepted name: ribosomal protein L3 N5-glutamine methyltransferase
Reaction: S-adenosyl-L-methionine + [ribosomal protein L3]-L-glutamine = S-adenosyl-L-homocysteine + [ribosomal protein L3]-N5-methyl-L-glutamine
Other name(s): YfcB; PrmB
Systematic name: S-adenosyl-L-methionine:[ribosomal protein L3]-L-glutamine (N5-glutamine)-methyltransferase
Comments: Modifies the glutamine residue in the glycylglycylglutamine (GGQ) motif of ribosomal protein L3 (Gln150 in the protein from the bacterium Escherichia coli). The enzyme does not act on peptide chain release factor 1 or 2.
References:
1.  Heurgue-Hamard, V., Champ, S., Engstrom, A., Ehrenberg, M. and Buckingham, R.H. The hemK gene in Escherichia coli encodes the N5-glutamine methyltransferase that modifies peptide release factors. EMBO J. 21 (2002) 769–778. [PMID: 11847124]
[EC 2.1.1.298 created 2014]
 
 
EC 2.1.1.299     
Accepted name: protein N-terminal monomethyltransferase
Reaction: S-adenosyl-L-methionine + N-terminal-(A,P,S)PK-[protein] = S-adenosyl-L-homocysteine + N-terminal-N-methyl-N-(A,P,S)PK-[protein]
Other name(s): NRMT2 (gene name); METTL11B (gene name); N-terminal monomethylase
Systematic name: S-adenosyl-L-methionine:N-terminal-(A,P,S)PK-[protein] monomethyltransferase
Comments: This enzyme methylates the N-terminus of target proteins containing the N-terminal motif [Ala/Pro/Ser]-Pro-Lys after the initiator L-methionine is cleaved. In contrast to EC 2.1.1.244, protein N-terminal methyltransferase, the protein only adds one methyl group to the N-terminal.
References:
1.  Petkowski, J.J., Bonsignore, L.A., Tooley, J.G., Wilkey, D.W., Merchant, M.L., Macara, I.G. and Schaner Tooley, C.E. NRMT2 is an N-terminal monomethylase that primes for its homologue NRMT1. Biochem. J. 456 (2013) 453–462. [PMID: 24090352]
[EC 2.1.1.299 created 2014]
 
 
EC 2.1.1.300     
Accepted name: pavine N-methyltransferase
Reaction: S-adenosyl-L-methionine + (±)-pavine = S-adenosyl-L-homocysteine + N-methylpavine
Other name(s): PavNMT
Systematic name: S-adenosyl-L-methionine:(±)-pavine N-methyltransferase
Comments: The enzyme, isolated from the plant Thalictrum flavum, also methylates (R,S)-stylopine and (S)-scoulerine (11%) with lower activity (14% and 11%, respectively).
References:
1.  Jain, A., Ziegler, J., Liscombe, D.K., Facchini, P.J., Tucker, P.A. and Panjikar, S. Purification, crystallization and X-ray diffraction analysis of pavine N-methyltransferase from Thalictrum flavum. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 64 (2008) 1066–1069. [PMID: 18997344]
2.  Liscombe, D.K., Ziegler, J., Schmidt, J., Ammer, C. and Facchini, P.J. Targeted metabolite and transcript profiling for elucidating enzyme function: isolation of novel N-methyltransferases from three benzylisoquinoline alkaloid-producing species. Plant J. 60 (2009) 729–743. [PMID: 19624470]
[EC 2.1.1.300 created 2014]
 
 
EC 2.1.1.301     
Accepted name: cypemycin N-terminal methyltransferase
Reaction: 2 S-adenosyl-L-methionine + N-terminal L-alanine-[cypemycin] = 2 S-adenosyl-L-homocysteine + N-terminal N,N-dimethyl-L-alanine-[cypemycin]
Other name(s): CypM
Systematic name: S-adenosyl-L-methionine:N-terminal L-alanine-[cypemycin] N-methyltransferase
Comments: The enzyme, isolated from the bacterium Streptomyces sp. OH-4156, can methylate a variety of linear oligopeptides, cyclic peptides such as nisin and haloduracin, and the ε-amino group of lysine [2]. Cypemycin is a peptide antibiotic, a member of the linaridins, a class of posttranslationally modified ribosomally synthesized peptides.
References:
1.  Claesen, J. and Bibb, M. Genome mining and genetic analysis of cypemycin biosynthesis reveal an unusual class of posttranslationally modified peptides. Proc. Natl. Acad. Sci. USA 107 (2010) 16297–16302. [PMID: 20805503]
2.  Zhang, Q. and van der Donk, W.A. Catalytic promiscuity of a bacterial α-N-methyltransferase. FEBS Lett. 586 (2012) 3391–3397. [PMID: 22841713]
[EC 2.1.1.301 created 2014]
 
 
EC 2.1.1.302     
Accepted name: 3-hydroxy-5-methyl-1-naphthoate 3-O-methyltransferase
Reaction: S-adenosyl-L-methionine + 3-hydroxy-5-methyl-1-naphthoate = S-adenosyl-L-homocysteine + 3-methoxy-5-methyl-1-naphthoate
Other name(s): AziB2
Systematic name: S-adenosyl-L-methionine:3-hydroxy-5-methyl-1-naphthoate 3-O-methyltransferase
Comments: The enzyme from the bacterium Streptomyces sahachiroi is involved in the biosynthesis of 3-methoxy-5-methyl-1-naphthoate, a component of of the the antitumor antibiotic azinomycin B.
References:
1.  Ding, W., Deng, W., Tang, M., Zhang, Q., Tang, G., Bi, Y. and Liu, W. Biosynthesis of 3-methoxy-5-methyl naphthoic acid and its incorporation into the antitumor antibiotic azinomycin B. Mol. Biosyst. 6 (2010) 1071–1081. [PMID: 20485749]
[EC 2.1.1.302 created 2014]
 
 
EC 2.1.1.303     
Accepted name: 2,7-dihydroxy-5-methyl-1-naphthoate 7-O-methyltransferase
Reaction: S-adenosyl-L-methionine + 2,7-dihydroxy-5-methyl-1-naphthoate = S-adenosyl-L-homocysteine + 2-hydroxy-7-methoxy-5-methyl-1-naphthoate
Other name(s): NcsB1; neocarzinostatin O-methyltransferase
Systematic name: S-adenosyl-L-methionine:2,7-dihydroxy-5-methyl-1-naphthoate 7-O-methyltransferase
Comments: The enzyme from the bacterium Streptomyces carzinostaticus is involved in the biosynthesis of 2-hydroxy-7-methoxy-5-methyl-1-naphthoate. This compound is part of the enediyne chromophore of the antitumor antibiotic neocarzinostatin. In vivo the enzyme catalyses the regiospecific methylation at the 7-hydroxy group of its native substrate 2,7-dihydroxy-5-methyl-1-naphthoate. In vitro it also recognizes other dihydroxynaphthoic acids and catalyses their regiospecific O-methylation.
References:
1.  Luo, Y., Lin, S., Zhang, J., Cooke, H.A., Bruner, S.D. and Shen, B. Regiospecific O-methylation of naphthoic acids catalyzed by NcsB1, an O-methyltransferase involved in the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin. J. Biol. Chem. 283 (2008) 14694–14702. [PMID: 18387946]
2.  Cooke, H.A., Guenther, E.L., Luo, Y., Shen, B. and Bruner, S.D. Molecular basis of substrate promiscuity for the SAM-dependent O-methyltransferase NcsB1, involved in the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin. Biochemistry 48 (2009) 9590–9598. [PMID: 19702337]
[EC 2.1.1.303 created 2014]
 
 
EC 2.1.1.304     
Accepted name: L-tyrosine C3-methyltransferase
Reaction: S-adenosyl-L-methionine + L-tyrosine = S-adenosyl-L-homocysteine + 3-methyl-L-tyrosine
Other name(s): SfmM2; SacF
Systematic name: S-adenosyl-L-methionine:L-tyrosine C3-methyltransferase
Comments: The enzyme from the bacterium Streptomyces lavendulae is involved in biosynthesis of saframycin A, a potent antitumor antibiotic that belongs to the tetrahydroisoquinoline family.
References:
1.  Tang, M.C., Fu, C.Y. and Tang, G.L. Characterization of SfmD as a heme peroxidase that catalyzes the regioselective hydroxylation of 3-methyltyrosine to 3-hydroxy-5-methyltyrosine in saframycin A biosynthesis. J. Biol. Chem. 287 (2012) 5112–5121. [PMID: 22187429]
[EC 2.1.1.304 created 2014]
 
 
EC 2.1.1.305     
Accepted name: 8-demethyl-8-α-L-rhamnosyltetracenomycin-C 2′-O-methyltransferase
Reaction: S-adenosyl-L-methionine + 8-demethyl-8-α-L-rhamnosyltetracenomycin C = S-adenosyl-L-homocysteine + 8-demethyl-8-(2-O-methyl-α-L-rhamnosyl)tetracenomycin C
Glossary: 8-demethyl-8-α-L-rhamnosyltetracenomycin C = methyl (6aR,7S,10aR)-6a,7,10a,12-tetrahydroxy-8-methoxy-1-methyl-6,10,11-trioxo-3-α-L-rhamnosyloxy-6,6a,7,10,10a,11-hexahydrotetracene-2-carboxylate
Other name(s): ElmMI
Systematic name: S-adenosyl-L-methionine:8-demethyl-8-α-L-rhamnosyltetracenomycin-C 2′-O-methyltransferase
Comments: The enzyme from the bacterium Streptomyces olivaceus is involved in the biosynthesis of the polyketide elloramycin.
References:
1.  Patallo, E.P., Blanco, G., Fischer, C., Brana, A.F., Rohr, J., Mendez, C. and Salas, J.A. Deoxysugar methylation during biosynthesis of the antitumor polyketide elloramycin by Streptomyces olivaceus. Characterization of three methyltransferase genes. J. Biol. Chem. 276 (2001) 18765–18774. [PMID: 11376004]
[EC 2.1.1.305 created 2014]
 
 
EC 2.1.1.306     
Accepted name: 8-demethyl-8-(2-methoxy-α-L-rhamnosyl)tetracenomycin-C 3′-O-methyltransferase
Reaction: S-adenosyl-L-methionine + 8-demethyl-8-(2-O-methyl-α-L-rhamnosyl)tetracenomycin C = S-adenosyl-L-homocysteine + 8-demethyl-8-(2,3-di-O-methyl-α-L-rhamnosyl)tetracenomycin C
Glossary: 8-demethyl-8-α-L-rhamnosyltetracenomycin C = methyl (6aR,7S,10aR)-6a,7,10a,12-tetrahydroxy-8-methoxy-1-methyl-6,10,11-trioxo-3-α-L-rhamnosyloxy-6,6a,7,10,10a,11-hexahydrotetracene-2-carboxylate
Other name(s): ElmMII
Systematic name: S-adenosyl-L-methionine:8-demethyl-8-(2-methoxy-α-L-rhamnosyl)tetracenomycin-C 3′-O-methyltransferase
Comments: The enzyme from the bacterium Streptomyces olivaceus is involved in the biosynthesis of the polyketide elloramycin.
References:
1.  Patallo, E.P., Blanco, G., Fischer, C., Brana, A.F., Rohr, J., Mendez, C. and Salas, J.A. Deoxysugar methylation during biosynthesis of the antitumor polyketide elloramycin by Streptomyces olivaceus. Characterization of three methyltransferase genes. J. Biol. Chem. 276 (2001) 18765–18774. [PMID: 11376004]
[EC 2.1.1.306 created 2014]
 
 
EC 2.1.1.307     
Accepted name: 8-demethyl-8-(2,3-dimethoxy-α-L-rhamnosyl)tetracenomycin-C 4′-O-methyltransferase
Reaction: S-adenosyl-L-methionine + 8-demethyl-8-(2,3-di-O-methyl-α-L-rhamnosyl)tetracenomycin C = S-adenosyl-L-homocysteine + 8-demethyl-8-(2,3,4-tri-O-methyl-α-L-rhamnosyl)tetracenomycin C
Glossary: 8-demethyl-8-α-L-rhamnosyltetracenomycin C = methyl (6aR,7S,10aR)-6a,7,10a,12-tetrahydroxy-8-methoxy-1-methyl-6,10,11-trioxo-3-α-L-rhamnosyloxy-6,6a,7,10,10a,11-hexahydrotetracene-2-carboxylate
Other name(s): ElmMIII
Systematic name: S-adenosyl-L-methionine:8-demethyl-8-(2,3-di-O-methoxy-α-L-rhamnosyl)tetracenomycin-C 4′-O-methyltransferase
Comments: The enzyme from the bacterium Streptomyces olivaceus is involved in the biosynthesis of the polyketide elloramycin.
References:
1.  Patallo, E.P., Blanco, G., Fischer, C., Brana, A.F., Rohr, J., Mendez, C. and Salas, J.A. Deoxysugar methylation during biosynthesis of the antitumor polyketide elloramycin by Streptomyces olivaceus. Characterization of three methyltransferase genes. J. Biol. Chem. 276 (2001) 18765–18774. [PMID: 11376004]
[EC 2.1.1.307 created 2014]
 
 
EC 2.1.1.308     
Accepted name: cytidylyl-2-hydroxyethylphosphonate methyltransferase
Reaction: 2 S-adenosyl-L-methionine + cytidine 5′-{[hydroxy(2-hydroxyethyl)phosphonoyl]phosphate} + reduced acceptor = S-adenosyl-L-homocysteine + 5′-deoxyadenosine + L-methionine + cytidine 5′-{[hydroxy(2-hydroxypropyl)phosphonoyl]phosphate} + oxidized acceptor
Other name(s): Fom3; S-adenosyl-L-methionine:methylcob(III)alamin:2-hydroxyethylphosphonate methyltransferase (incorrect); 2-hydroxyethylphosphonate methyltransferase (incorrect)
Systematic name: S-adenosyl-L-methionine:cytidine 5′-{[hydroxy(2-hydroxyethyl)phosphonoyl]phosphate} C-methyltransferase
Comments: Requires cobalamin. The enzyme, isolated from the bacterium Streptomyces wedmorensis, is involved in fosfomycin biosynthesis. It is a radical S-adenosyl-L-methionine (SAM) enzyme that contains a [4Fe-4S] center and a methylcob(III)alamin cofactor. The enzyme uses two molecues of SAM for the reaction. One molecule forms a 5′-deoxyadenosyl radical, while the other is used to methylate the cobalamin cofactor. The 5′-deoxyadenosyl radical abstracts a hydrogen from the C2 position of cytidine 5′-{[(2-hydroxyethyl)phosphonoyl]phosphate} forming a free radical that reacts with the methyl group on methylcob(III)alamin at the opposite side from SAM and the [4Fe-4S] cluster to produce a racemic mix of methylated products and cob(II)alamin. Both the [4Fe-4S] cluster and the cob(II)alamin need to be reduced by an unknown factor(s) before the enzyme could catalyse another cycle.
References:
1.  Woodyer, R.D., Li, G., Zhao, H. and van der Donk, W.A. New insight into the mechanism of methyl transfer during the biosynthesis of fosfomycin. Chem. Commun. (Camb.) (2007) 359–361. [PMID: 17220970]
2.  Allen, K.D. and Wang, S.C. Initial characterization of Fom3 from Streptomyces wedmorensis: The methyltransferase in fosfomycin biosynthesis. Arch. Biochem. Biophys. 543 (2014) 67–73. [PMID: 24370735]
3.  Sato, S., Kudo, F., Kim, S.Y., Kuzuyama, T. and Eguchi, T. Methylcobalamin-dependent radical SAM C-methyltransferase Fom3 recognizes cytidylyl-2-hydroxyethylphosphonate and catalyzes the nonstereoselective C-methylation in fosfomycin biosynthesis. Biochemistry 56 (2017) 3519–3522. [PMID: 28678474]
4.  Blaszczyk, A.J. and Booker, S.J. A (re)discovery of the Fom3 substrate. Biochemistry 57 (2018) 891–892. [PMID: 29345912]
[EC 2.1.1.308 created 2014, modified 2019]
 
 
EC 2.1.1.309     
Accepted name: 18S rRNA (guanine1575-N7)-methyltransferase
Reaction: S-adenosyl-L-methionine + guanine1575 in 18S rRNA = S-adenosyl-L-homocysteine + N7-methylguanine1575 in 18S rRNA
Other name(s): 18S rRNA methylase Bud23; BUD23 (gene name)
Systematic name: S-adenosyl-L-methionine:18S rRNA (guanine1575-N7)-methyltransferase
Comments: The enzyme, found in eukaryotes, is involved in pre-rRNA processing. The numbering corresponds to the enzyme from the yeast Saccharomyces cerevisiae [1].
References:
1.  White, J., Li, Z., Sardana, R., Bujnicki, J.M., Marcotte, E.M. and Johnson, A.W. Bud23 methylates G1575 of 18S rRNA and is required for efficient nuclear export of pre-40S subunits. Mol. Cell Biol. 28 (2008) 3151–3161. [PMID: 18332120]
[EC 2.1.1.309 created 2014]
 
 
EC 2.1.1.310     
Accepted name: 25S rRNA (cytosine2870-C5)-methyltransferase
Reaction: S-adenosyl-L-methionine + cytosine2870 in 25S rRNA = S-adenosyl-L-homocysteine + 5-methylcytosine2870 in 25S rRNA
Other name(s): NOP2 (gene name)
Systematic name: S-adenosyl-L-methionine:25S rRNA (cytosine2870-C5)-methyltransferase
Comments: The enzyme, found in eukaryotes, is specific for cytosine2870 of the 25S ribosomal RNA. The numbering corresponds to the enzyme from the yeast Saccharomyces cerevisiae [1].
References:
1.  Sharma, S., Yang, J., Watzinger, P., Kotter, P. and Entian, K.D. Yeast Nop2 and Rcm1 methylate C2870 and C2278 of the 25S rRNA, respectively. Nucleic Acids Res. 41 (2013) 9062–9076. [PMID: 23913415]
[EC 2.1.1.310 created 2014]
 
 
EC 2.1.1.311     
Accepted name: 25S rRNA (cytosine2278-C5)-methyltransferase
Reaction: S-adenosyl-L-methionine + cytosine2278 in 25S rRNA = S-adenosyl-L-homocysteine + 5-methylcytosine2278 in 25S rRNA
Other name(s): RCM1 (gene name)
Systematic name: S-adenosyl-L-methionine:25S rRNA (cytosine2278-C5)-methyltransferase
Comments: The enzyme, found in eukaryotes, is specific for 25S cytosine2278. The numbering corresponds to the enzyme from the yeast Saccharomyces cerevisiae [1].
References:
1.  Sharma, S., Yang, J., Watzinger, P., Kotter, P. and Entian, K.D. Yeast Nop2 and Rcm1 methylate C2870 and C2278 of the 25S rRNA, respectively. Nucleic Acids Res. 41 (2013) 9062–9076. [PMID: 23913415]
[EC 2.1.1.311 created 2014]
 
 
EC 2.1.1.312     
Accepted name: 25S rRNA (uracil2843-N3)-methyltransferase
Reaction: S-adenosyl-L-methionine + uracil2843 in 25S rRNA = S-adenosyl-L-homocysteine + N3-methyluracil2843 in 25S rRNA
Other name(s): BMT6
Systematic name: S-adenosyl-L-methionine:tRNA (uracil2843-N3)-methyltransferase
Comments: The enzyme, described from the yeast Saccharomyces cerevisiae, is involved in ribosome biogenesis.
References:
1.  Sharma, S., Yang, J., Duttmann, S., Watzinger, P., Kotter, P. and Entian, K.D. Identification of novel methyltransferases, Bmt5 and Bmt6, responsible for the m3U methylations of 25S rRNA in Saccharomyces cerevisiae. Nucleic Acids Res. 42 (2014) 3246–3260. [PMID: 24335083]
[EC 2.1.1.312 created 2014]
 
 
EC 2.1.1.313     
Accepted name: 25S rRNA (uracil2634-N3)-methyltransferase
Reaction: S-adenosyl-L-methionine + uracil2634 in 25S rRNA = S-adenosyl-L-homocysteine + N3-methyluracil2634 in 25S rRNA
Other name(s): BMT5
Systematic name: S-adenosyl-L-methionine:tRNA (uracil2634-N3)-methyltransferase
Comments: The enzyme, described from the yeast Saccharomyces cerevisiae, is involved in ribosome biogenesis.
References:
1.  Sharma, S., Yang, J., Duttmann, S., Watzinger, P., Kotter, P. and Entian, K.D. Identification of novel methyltransferases, Bmt5 and Bmt6, responsible for the m3U methylations of 25S rRNA in Saccharomyces cerevisiae. Nucleic Acids Res. 42 (2014) 3246–3260. [PMID: 24335083]
[EC 2.1.1.313 created 2014]
 
 
EC 2.1.1.314     
Accepted name: diphthine methyl ester synthase
Reaction: 4 S-adenosyl-L-methionine + 2-[(3S)-3-carboxy-3-aminopropyl]-L-histidine-[translation elongation factor 2] = 4 S-adenosyl-L-homocysteine + diphthine methyl ester-[translation elongation factor 2]
Glossary: diphthine methyl ester = 2-[(3S)-4-methoxy-4-oxo-3-(trimethylammonio)butyl]-L-histidine
Other name(s): S-adenosyl-L-methionine:elongation factor 2 methyltransferase (ambiguous); diphthine methyltransferase (ambiguous); Dph5 (ambiguous)
Systematic name: S-adenosyl-L-methionine:2-[(3S)-3-carboxy-3-aminopropyl]-L-histidine-[translation elongation factor 2] methyltransferase (diphthine methyl ester-[translation elongation factor 2]-forming)
Comments: This eukaryotic enzyme is part of the biosynthetic pathway of diphthamide. Different from the archaeal enzyme, which performs only 3 methylations, producing diphthine (cf. EC 2.1.1.98). The relevant histidine of elongation factor 2 is His715 in mammals and His699 in yeast. The order of the 4 methylations is not known.
References:
1.  Chen, J.-Y.C. and Bodley, J.W. Biosynthesis of diphthamide in Saccharomyces cerevisiae. Partial purification and characterization of a specific S-adenosylmethionine:elongation factor 2 methyltransferase. J. Biol. Chem. 263 (1988) 11692–11696. [PMID: 3042777]
2.  Moehring, J.M. and Moehring, T.J. The post-translational trimethylation of diphthamide studied in vitro. J. Biol. Chem. 263 (1988) 3840–3844. [PMID: 3346227]
3.  Lin, Z., Su, X., Chen, W., Ci, B., Zhang, S. and Lin, H. Dph7 catalyzes a previously unknown demethylation step in diphthamide biosynthesis. J. Am. Chem. Soc. 136 (2014) 6179–6182. [PMID: 24739148]
[EC 2.1.1.314 created 2015]
 
 
EC 2.1.1.315     
Accepted name: 27-O-demethylrifamycin SV methyltransferase
Reaction: S-adenosyl-L-methionine + 27-O-demethylrifamycin SV = S-adenosyl-L-homocysteine + rifamycin SV
Glossary: rifamycin SV = (7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-2,15,17,27,29-pentahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-6,23-dioxo-8,30-dioxa-24-azatetracyclo[23.3.1.14,7.05,28]triaconta-1(28),2,4,9, 19,21,25(29),26-octaen-13-yl acetate
Other name(s): AdoMet:27-O-demethylrifamycin SV methyltransferase
Systematic name: S-adenosyl-L-methionine:27-O-demethylrifamycin-SV 27-O-methyltransferase
Comments: The enzyme, characterized from the bacterium Amycolatopsis mediterranei, is involved in biosynthesis of the antitubercular drug rifamycin B.
References:
1.  Xu, J., Mahmud, T. and Floss, H.G. Isolation and characterization of 27-O-demethylrifamycin SV methyltransferase provides new insights into the post-PKS modification steps during the biosynthesis of the antitubercular drug rifamycin B by Amycolatopsis mediterranei S699. Arch. Biochem. Biophys. 411 (2003) 277–288. [PMID: 12623077]
[EC 2.1.1.315 created 2015]
 
 
EC 2.1.1.316     
Accepted name: mitomycin 6-O-methyltransferase
Reaction: (1) S-adenosyl-L-methionine + 6-demethylmitomycin A = S-adenosyl-L-homocysteine + mitomycin A
(2) S-adenosyl-L-methionine + 6-demethylmitomycin B = S-adenosyl-L-homocysteine + mitomycin B
Glossary: mitomycin A = [(1aS,8S,8aR,8bS)-5-methyl-6,8a-dimethoxy-4,7-dioxo-1,1a,2,4,7,8,8a,8b-octahydroazirino[2′,3′:3,4]pyrrolo[1,2-a]indol-8-yl]methyl carbamate
mitomycin B = [(1aS,8S,8aR,8bS)-8a-hydroxy-5-methyl-6-methoxy-4,7-dioxo-1,1a,2,4,7,8,8a,8b-octahydroazirino[2′,3′:3,4]pyrrolo[1,2-a]indol-8-yl]methyl carbamate
Other name(s): MmcR; mitomycin 7-O-methyltransferase (incorrect); S-adenosyl-L-methionine:7-demethylmitomycin-A 7-O-methyltransferase (incorrect)
Systematic name: S-adenosyl-L-methionine:6-demethylmitomycin-A 6-O-methyltransferase
Comments: The enzyme, characterized from the bacterium Streptomyces lavendulae, is involved in the biosynthesis of the quinone-containing antibiotics mitomycin A and mitomycin B.
References:
1.  Gruschow, S., Chang, L.C., Mao, Y. and Sherman, D.H. Hydroxyquinone O-methylation in mitomycin biosynthesis. J. Am. Chem. Soc. 129 (2007) 6470–6476. [PMID: 17461583]
2.  Singh, S., Chang, A., Goff, R.D., Bingman, C.A., Gruschow, S., Sherman, D.H., Phillips, G.N., Jr. and Thorson, J.S. Structural characterization of the mitomycin 7-O-methyltransferase. Proteins 79 (2011) 2181–2188. [PMID: 21538548]
[EC 2.1.1.316 created 2015]
 
 
EC 2.1.1.317     
Accepted name: sphingolipid C9-methyltransferase
Reaction: S-adenosyl-L-methionine + a (4E,8E)-sphinga-4,8-dienine ceramide = S-adenosyl-L-homocysteine + a 9-methyl-(4E,8E)-sphinga-4,8-dienine ceramide
Systematic name: S-adenosyl-L-methionine:(4E,8E)-sphinga-4,8-dienine ceramide C-methyltransferase
Comments: The enzyme, characterized from the fungi Komagataella pastoris and Fusarium graminearum, acts only on ceramides and has no activity with free sphingoid bases or glucosylceramides.
References:
1.  Ternes, P., Sperling, P., Albrecht, S., Franke, S., Cregg, J.M., Warnecke, D. and Heinz, E. Identification of fungal sphingolipid C9-methyltransferases by phylogenetic profiling. J. Biol. Chem. 281 (2006) 5582–5592. [PMID: 16339149]
2.  Ramamoorthy, V., Cahoon, E.B., Thokala, M., Kaur, J., Li, J. and Shah, D.M. Sphingolipid C-9 methyltransferases are important for growth and virulence but not for sensitivity to antifungal plant defensins in Fusarium graminearum. Eukaryot Cell 8 (2009) 217–229. [PMID: 19028992]
[EC 2.1.1.317 created 2015]
 
 
EC 2.1.1.318     
Accepted name: [trehalose-6-phosphate synthase]-L-cysteine S-methyltransferase
Reaction: S-adenosyl-L-methionine + [trehalose-6-phosphate synthase]-L-cysteine = S-adenosyl-L-homocysteine + [trehalose-6-phosphate synthase]-S-methyl-L-cysteine
Systematic name: S-adenosyl-L-methionine:[trehalose-6-phosphate synthase]-L-cysteine S-methyltransferase
Comments: The enzyme, characterized from the yeast Saccharomyces cerevisiae, enhances the activity of EC 2.4.1.15, trehalose-6-phosphate synthase, resulting in elevating the levels of trehalose in the cell and contributing to stationary phase survival. In vitro the enzyme performs S-methylation of L-cysteine residues of various protein substrates.
References:
1.  Sengupta, S., Banerjee, S., Lahiri, S., Dutta, T., Dhar, T.K. and Ghosh, A.K. Purification, characterization, sequencing and molecular cloning of a novel cysteine methyltransferase that regulates trehalose-6-phosphate synthase from Saccharomyces cerevisiae. Biochim. Biophys. Acta 1840 (2014) 1861–1871. [PMID: 24412193]
[EC 2.1.1.318 created 2015]
 
 
EC 2.1.1.319     
Accepted name: type I protein arginine methyltransferase
Reaction: 2 S-adenosyl-L-methionine + [protein]-L-arginine = 2 S-adenosyl-L-homocysteine + [protein]-Nω,Nω-dimethyl-L-arginine (overall reaction)
(1a) S-adenosyl-L-methionine + [protein]-L-arginine = S-adenosyl-L-homocysteine + [protein]-Nω-methyl-L-arginine
(1b) S-adenosyl-L-methionine + [protein]-Nω-methyl-L-arginine = S-adenosyl-L-homocysteine + [protein]-Nω,Nω-dimethyl-L-arginine
Other name(s): PRMT1 (gene name); PRMT2 (gene name); PRMT3 (gene name); PRMT4 (gene name); PRMT6 (gene name); PRMT8 (gene name); RMT1 (gene name); CARM1 (gene name)
Systematic name: S-adenosyl-L-methionine:[protein]-L-arginine N-methyltransferase ([protein]-Nω,Nω-dimethyl-L-arginine-forming)
Comments: This eukaryotic enzyme catalyses the sequential dimethylation of one of the terminal guanidino nitrogen atoms in arginine residues, resulting in formation of asymmetric dimethylarginine residues. Some forms (e.g. PRMT1) have a very wide substrate specificity, while others (e.g. PRMT4 and PRMT6) are rather specific. The enzyme has a preference for methylating arginine residues that are flanked by one or more glycine residues [1]. PRMT1 is responsible for the bulk (about 85%) of total protein arginine methylation activity in mammalian cells [2]. cf. EC 2.1.1.320, type II protein arginine methyltransferase, EC 2.1.1.321, type III protein arginine methyltransferase, and EC 2.1.1.322, type IV protein arginine methyltransferase.
References:
1.  Gary, J.D. and Clarke, S. RNA and protein interactions modulated by protein arginine methylation. Prog. Nucleic Acid Res. Mol. Biol. 61 (1998) 65–131. [PMID: 9752719]
2.  Tang, J., Gary, J.D., Clarke, S. and Herschman, H.R. PRMT 3, a type I protein arginine N-methyltransferase that differs from PRMT1 in its oligomerization, subcellular localization, substrate specificity, and regulation. J. Biol. Chem. 273 (1998) 16935–16945. [PMID: 9642256]
3.  Tang, J., Frankel, A., Cook, R.J., Kim, S., Paik, W.K., Williams, K.R., Clarke, S. and Herschman, H.R. PRMT1 is the predominant type I protein arginine methyltransferase in mammalian cells. J. Biol. Chem. 275 (2000) 7723–7730. [PMID: 10713084]
4.  Frankel, A., Yadav, N., Lee, J., Branscombe, T.L., Clarke, S. and Bedford, M.T. The novel human protein arginine N-methyltransferase PRMT6 is a nuclear enzyme displaying unique substrate specificity. J. Biol. Chem. 277 (2002) 3537–3543. [PMID: 11724789]
[EC 2.1.1.319 created 2015]
 
 
EC 2.1.1.320     
Accepted name: type II protein arginine methyltransferase
Reaction: 2 S-adenosyl-L-methionine + [protein]-L-arginine = 2 S-adenosyl-L-homocysteine + [protein]-Nω,Nω′-dimethyl-L-arginine (overall reaction)
(1a) S-adenosyl-L-methionine + [protein]-L-arginine = S-adenosyl-L-homocysteine + [protein]-Nω-methyl-L-arginine
(1b) S-adenosyl-L-methionine + [protein]-Nω-methyl-L-arginine = S-adenosyl-L-homocysteine + [protein]-Nω,Nω′-dimethyl-L-arginine
Other name(s): PRMT5 (gene name); PRMT9 (gene name)
Systematic name: S-adenosyl-L-methionine:[protein]-L-arginine N-methyltransferase ([protein]-Nω,Nω′-dimethyl-L-arginine-forming)
Comments: The enzyme catalyses the methylation of one of the terminal guanidino nitrogen atoms in arginine residues within proteins, forming monomethylarginine, followed by the methylation of the second terminal nitrogen atom to form a symmetrical dimethylarginine. The mammalian enzyme is active in both the nucleus and the cytoplasm, and plays a role in the assembly of snRNP core particles by methylating certain small nuclear ribonucleoproteins. cf. EC 2.1.1.319, type I protein arginine methyltransferase, EC 2.1.1.321, type III protein arginine methyltransferase, and EC 2.1.1.322, type IV protein arginine methyltransferase.
References:
1.  Branscombe, T.L., Frankel, A., Lee, J.H., Cook, J.R., Yang, Z., Pestka, S. and Clarke, S. PRMT5 (Janus kinase-binding protein 1) catalyzes the formation of symmetric dimethylarginine residues in proteins. J. Biol. Chem. 276 (2001) 32971–32976. [PMID: 11413150]
2.  Wang, X., Zhang, Y., Ma, Q., Zhang, Z., Xue, Y., Bao, S. and Chong, K. SKB1-mediated symmetric dimethylation of histone H4R3 controls flowering time in Arabidopsis. EMBO J. 26 (2007) 1934–1941. [PMID: 17363895]
3.  Lacroix, M., El Messaoudi, S., Rodier, G., Le Cam, A., Sardet, C. and Fabbrizio, E. The histone-binding protein COPR5 is required for nuclear functions of the protein arginine methyltransferase PRMT5. EMBO Rep. 9 (2008) 452–458. [PMID: 18404153]
4.  Chari, A., Golas, M.M., Klingenhager, M., Neuenkirchen, N., Sander, B., Englbrecht, C., Sickmann, A., Stark, H. and Fischer, U. An assembly chaperone collaborates with the SMN complex to generate spliceosomal SnRNPs. Cell 135 (2008) 497–509. [PMID: 18984161]
5.  Antonysamy, S., Bonday, Z., Campbell, R.M., Doyle, B., Druzina, Z., Gheyi, T., Han, B., Jungheim, L.N., Qian, Y., Rauch, C., Russell, M., Sauder, J.M., Wasserman, S.R., Weichert, K., Willard, F.S., Zhang, A. and Emtage, S. Crystal structure of the human PRMT5:MEP50 complex. Proc. Natl. Acad. Sci. USA 109 (2012) 17960–17965. [PMID: 23071334]
6.  Hadjikyriacou, A., Yang, Y., Espejo, A., Bedford, M.T. and Clarke, S.G. Unique features of human protein arginine methyltransferase 9 (PRMT9) and its substrate RNA splicing factor SF3B2. J. Biol. Chem. 290 (2015) 16723–16743. [PMID: 25979344]
[EC 2.1.1.320 created 2015]
 
 
EC 2.1.1.321     
Accepted name: type III protein arginine methyltransferase
Reaction: S-adenosyl-L-methionine + [protein]-L-arginine = S-adenosyl-L-homocysteine + [protein]-Nω-methyl-L-arginine
Other name(s): PRMT7 (gene name)
Systematic name: S-adenosyl-L-methionine:[protein]-L-arginine N-methyltransferase ([protein]-Nω-methyl-L-arginine-forming)
Comments: Type III protein arginine methyltransferases catalyse the single methylation of one of the terminal nitrogen atoms of the guanidino group in an L-arginine residue within a protein. Unlike type I and type II protein arginine methyltransferases, which also catalyse this reaction, type III enzymes do not methylate the substrate any further. cf. EC 2.1.1.319, type I protein arginine methyltransferase, EC 2.1.1.320, type II protein arginine methyltransferase, and EC 2.1.1.322, type IV protein arginine methyltransferase.
References:
1.  Miranda, T.B., Miranda, M., Frankel, A. and Clarke, S. PRMT7 is a member of the protein arginine methyltransferase family with a distinct substrate specificity. J. Biol. Chem. 279 (2004) 22902–22907. [PMID: 15044439]
2.  Gonsalvez, G.B., Tian, L., Ospina, J.K., Boisvert, F.M., Lamond, A.I. and Matera, A.G. Two distinct arginine methyltransferases are required for biogenesis of Sm-class ribonucleoproteins. J. Cell Biol. 178 (2007) 733–740. [PMID: 17709427]
3.  Feng, Y., Hadjikyriacou, A. and Clarke, S.G. Substrate specificity of human protein arginine methyltransferase 7 (PRMT7): the importance of acidic residues in the double E loop. J. Biol. Chem. 289 (2014) 32604–32616. [PMID: 25294873]
[EC 2.1.1.321 created 2015]
 
 
EC 2.1.1.322     
Accepted name: type IV protein arginine methyltransferase
Reaction: S-adenosyl-L-methionine + [protein]-L-arginine = S-adenosyl-L-homocysteine + [protein]-N5-methyl-L-arginine
Other name(s): RMT2 (gene name)
Systematic name: S-adenosyl-L-methionine:[protein]-L-arginine N-methyltransferase ([protein]-N5-methyl-L-arginine-forming)
Comments: This enzyme, characterized from the yeast Saccharomyces cerevisiae, methylates the the δ-nitrogen atom of arginine residues within proteins. Among its substrates are Arg67 of the ribosomal protein L12. cf. EC 2.1.1.319, type I protein arginine methyltransferase, EC 2.1.1.320, type II protein arginine methyltransferase, and EC 2.1.1.321, type III protein arginine methyltransferase.
References:
1.  Niewmierzycka, A. and Clarke, S. S-Adenosylmethionine-dependent methylation in Saccharomyces cerevisiae. Identification of a novel protein arginine methyltransferase. J. Biol. Chem. 274 (1999) 814–824. [PMID: 9873020]
2.  Chern, M.K., Chang, K.N., Liu, L.F., Tam, T.C., Liu, Y.C., Liang, Y.L. and Tam, M.F. Yeast ribosomal protein L12 is a substrate of protein-arginine methyltransferase 2. J. Biol. Chem. 277 (2002) 15345–15353. [PMID: 11856739]
3.  Olsson, I., Berrez, J.M., Leipus, A., Ostlund, C. and Mutvei, A. The arginine methyltransferase Rmt2 is enriched in the nucleus and co-purifies with the nuclear porins Nup49, Nup57 and Nup100. Exp. Cell Res. 313 (2007) 1778–1789. [PMID: 17448464]
[EC 2.1.1.322 created 2015]
 
 
EC 2.1.1.323     
Accepted name: (–)-pluviatolide 4-O-methyltransferase
Reaction: S-adenosyl-L-methionine + (–)-pluviatolide = S-adenosyl-L-homocysteine + (–)-bursehernin
Glossary: (–)-pluviatolide = (3R,4R)-4-(2H-1,3-benzodioxol-5-ylmethyl)-3-[(4-hydroxy-3-methoxyphenyl)methyl]oxolan-2-one
(–)-bursehernin = (3R,4R)-4-(2H-1,3-benzodioxol-5-ylmethyl)-3-[(3,4-dimethoxyphenyl)methyl]oxolan-2-one
Other name(s): OMT3 (gene name)
Systematic name: S-adenosyl-L-methionine:(–)-pluviatolide 4-O-methyltransferase
Comments: The enzyme, characterized from the plant Sinopodophyllum hexandrum, is involved in the biosynthetic pathway of podophyllotoxin, a non-alkaloid toxin lignan whose derivatives are important anticancer drugs.
References:
1.  Lau, W. and Sattely, E.S. Six enzymes from mayapple that complete the biosynthetic pathway to the etoposide aglycone. Science 349 (2015) 1224–1228. [PMID: 26359402]
[EC 2.1.1.323 created 2016]
 
 
EC 2.1.1.324     
Accepted name: dTDP-4-amino-2,3,4,6-tetradeoxy-D-glucose N,N-dimethyltransferase
Reaction: 2 S-adenosyl-L-methionine + dTDP-4-amino-2,3,4,6-tetradeoxy-α-D-erythro-hexopyranose = 2 S-adenosyl-L-homocysteine + dTDP-α-D-forosamine (overall reaction)
(1a) S-adenosyl-L-methionine + dTDP-4-amino-2,3,4,6-tetradeoxy-α-D-erythro-hexopyranose = S-adenosyl-L-homocysteine + dTDP-4-(methylamino)-2,3,4,6-tetradeoxy-α-D-erythro-hexopyranose
(1b) S-adenosyl-L-methionine + dTDP-4-(methylamino)-2,3,4,6-tetradeoxy-α-D-erythro-hexopyranose = S-adenosyl-L-homocysteine + dTDP-α-D-forosamine
Glossary: dTDP-α-D-forosamine = dTDP-4-(dimethylamino)-2,3,4,6-tetradeoxy-α-D-erythro-hexopyranose
Other name(s): SpnS; TDP-4-amino-2,3,6-trideoxy-D-glucose N,N-dimethyltransferase
Systematic name: S-adenosyl-L-methionine:dTDP-4-amino-2,3,4,6-tetradeoxy-α-D-erythro-hexopyranose N,N-dimethyltransferase
Comments: The enzyme was isolated from the bacterium Saccharopolyspora spinosa, where it is involved in the biosynthesis of spinosyn A, an active ingredient of several commercial insecticides.
References:
1.  Hong, L., Zhao, Z., Melancon, C.E., 3rd, Zhang, H. and Liu, H.W. In vitro characterization of the enzymes involved in TDP-D-forosamine biosynthesis in the spinosyn pathway of Saccharopolyspora spinosa. J. Am. Chem. Soc. 130 (2008) 4954–4967. [PMID: 18345667]
[EC 2.1.1.324 created 2016]
 
 
EC 2.1.1.325     
Accepted name: juvenile hormone-III synthase
Reaction: (1) S-adenosyl-L-methionine + (2E,6E)-farnesoate = S-adenosyl-L-homocysteine + methyl (2E,6E)-farnesoate
(2) S-adenosyl-L-methionine + juvenile hormone III acid = S-adenosyl-L-homocysteine + juvenile hormone III
Glossary: juvenile hormone III = methyl (2E,6E,10R)-10,11-epoxy-3,7,11-trimethyldodeca-2,6-dienoate
juvenile hormone III acid = (2E,6E,10R)-10,11-epoxy-3,7,11-trimethyldodeca-2,6-dienoate
Other name(s): farnesoic acid methyltransferase; juvenile hormone acid methyltransferase; JHAMT
Systematic name: S-adenosyl-L-methionine:(2E,6E)-farnesoate O-methyltransferase
Comments: The enzyme, found in insects, is involved in the synthesis of juvenile hormone III, a sesquiterpenoid that regulates several processes including embryonic development, metamorphosis, and reproduction, in many insect species.
References:
1.  Shinoda, T. and Itoyama, K. Juvenile hormone acid methyltransferase: a key regulatory enzyme for insect metamorphosis. Proc. Natl. Acad. Sci. USA 100 (2003) 11986–11991. [PMID: 14530389]
2.  Defelipe, L.A., Dolghih, E., Roitberg, A.E., Nouzova, M., Mayoral, J.G., Noriega, F.G. and Turjanski, A.G. Juvenile hormone synthesis: "esterify then epoxidize" or "epoxidize then esterify"? Insights from the structural characterization of juvenile hormone acid methyltransferase. Insect Biochem. Mol. Biol. 41 (2011) 228–235. [PMID: 21195763]
3.  Van Ekert, E., Heylen, K., Rouge, P., Powell, C.A., Shatters, R.G., Jr., Smagghe, G. and Borovsky, D. Aedes aegypti juvenile hormone acid methyl transferase, the ultimate enzyme in the biosynthetic pathway of juvenile hormone III, exhibits substrate control. J. Insect Physiol. 64 (2014) 62–73. [PMID: 24657668]
4.  Van Ekert, E., Shatters, R.G., Jr., Rouge, P., Powell, C.A., Smagghe, G. and Borovsky, D. Cloning and expressing a highly functional and substrate specific farnesoic acid o-methyltransferase from the Asian citrus psyllid (Diaphorina citri Kuwayama). FEBS Open Bio 5 (2015) 264–275. [PMID: 25893162]
[EC 2.1.1.325 created 2016]
 
 
EC 2.1.1.326     
Accepted name: N-acetyldemethylphosphinothricin P-methyltransferase
Reaction: 2 S-adenosyl-L-methionine + N-acetyldemethylphosphinothricin + reduced acceptor = S-adenosyl-L-homocysteine + 5′-deoxyadenosine + L-methionine + N-acetylphosphinothricin + oxidized acceptor
Glossary: N-acetyldemethylphosphinothricin = (2S)-2-acetamido-4-phosphinatobutanoate
Other name(s): phpK (gene name); bcpD (gene name); P-methylase
Systematic name: S-adenosyl-L-methionine:N-acetyldemethylphosphinothricin P-methyltransferase
Comments: The enzyme was originally characterized from bacteria that produce the tripeptides bialaphos and phosalacine, which inhibit plant and bacterial glutamine synthetases. It is a radical S-adenosyl-L-methionine (SAM) enzyme that contains a [4Fe-4S] center and a methylcob(III)alamin cofactor. According to the proposed mechanism, the reduced iron-sulfur center donates an electron to SAM, resulting in homolytic cleavage of the carbon-sulfur bond to form a 5′-deoxyadenosyl radical that abstracts the hydrogen atom from the P-H bond of the substrate, forming a phosphinate-centered radical. This radical reacts with methylcob(III)alamin to produce the methylated product and cob(II)alamin, which is reduced by an unknown donor to cob(I)alamin. A potential route for restoring the latter back to methylcob(III)alamin is a nucleophilic attack on a second SAM molecule. The enzyme acts in vivo on N-acetyldemethylphosphinothricin-L-alanyl-L-alanine or N-acetyl-demethylphosphinothricin-L-alanyl-L-leucine, the intermediates in the biosynthesis of bialaphos and phosalacine, respectively. This transformation produces the only example of a carbon-phosphorus-carbon linkage known to occur in nature.
References:
1.  Kamigiri, K., Hidaka, T., Imai, S., Murakami, T. and Seto, H. Studies on the biosynthesis of bialaphos (SF-1293) 12. C-P bond formation mechanism of bialaphos: discovery of a P-methylation enzyme. J. Antibiot. (Tokyo) 45 (1992) 781–787. [PMID: 1624380]
2.  Hidaka, T., Hidaka, M., Kuzuyama, T. and Seto, H. Sequence of a P-methyltransferase-encoding gene isolated from a bialaphos-producing Streptomyces hygroscopicus. Gene 158 (1995) 149–150. [PMID: 7789803]
3.  Werner, W.J., Allen, K.D., Hu, K., Helms, G.L., Chen, B.S. and Wang, S.C. In vitro phosphinate methylation by PhpK from Kitasatospora phosalacinea. Biochemistry 50 (2011) 8986–8988. [PMID: 21950770]
4.  Allen, K.D. and Wang, S.C. Spectroscopic characterization and mechanistic investigation of P-methyl transfer by a radical SAM enzyme from the marine bacterium Shewanella denitrificans OS217. Biochim. Biophys. Acta 1844 (2014) 2135–2144. [PMID: 25224746]
5.  Hu, K., Werner, W.J., Allen, K.D. and Wang, S.C. Investigation of enzymatic C-P bond formation using multiple quantum HCP nuclear magnetic resonance spectroscopy. Magn. Reson. Chem. 53 (2015) 267–272. [PMID: 25594737]
[EC 2.1.1.326 created 2016]
 
 
EC 2.1.1.327     
Accepted name: phenazine-1-carboxylate N-methyltransferase
Reaction: S-adenosyl-L-methionine + phenazine-1-carboxylate = S-adenosyl-L-homocysteine + 5-methylphenazine-1-carboxylate
Other name(s): phzM (gene name)
Systematic name: S-adenosyl-L-methionine:phenazine-1-carboxylate 5-methyltransferase
Comments: The enzyme, characterized from the bacterium Pseudomonas aeruginosa, is involved in the biosynthesis of pyocyanin, a toxin produced and secreted by the organism. The enzyme is active in vitro only in the presence of EC 1.14.13.218, 5-methylphenazine-1-carboxylate 1-monooxygenase.
References:
1.  Parsons, J.F., Greenhagen, B.T., Shi, K., Calabrese, K., Robinson, H. and Ladner, J.E. Structural and functional analysis of the pyocyanin biosynthetic protein PhzM from Pseudomonas aeruginosa. Biochemistry 46 (2007) 1821–1828. [PMID: 17253782]
[EC 2.1.1.327 created 2016]
 
 
EC 2.1.1.328     
Accepted name: N-demethylindolmycin N-methyltransferase
Reaction: S-adenosyl-L-methionine + N-demethylindolmycin = S-adenosyl-L-homocysteine + indolmycin
Glossary: indolmycin = (5S)-5-[(1R)-1-(indol-3-yl)ethyl]-2-(methylamino)-1,3-oxazolin-4(5H)-one
Other name(s): ind7 (gene name)
Systematic name: S-adenosyl-L-methionine:N-demethylindolmycin N-methyltransferase
Comments: The enzyme, characterized from the bacterium Streptomyces griseus, catalyses the ultimate reaction in the biosynthesis of indolmycin, an antibacterial drug that inhibits the bacterial tryptophan—tRNA ligase (EC 6.1.1.2).
References:
1.  Du, Y.L., Alkhalaf, L.M. and Ryan, K.S. In vitro reconstitution of indolmycin biosynthesis reveals the molecular basis of oxazolinone assembly. Proc. Natl. Acad. Sci. USA 112 (2015) 2717–2722. [PMID: 25730866]
[EC 2.1.1.328 created 2016]
 
 
EC 2.1.1.329     
Accepted name: demethylphylloquinol methyltransferase
Reaction: S-adenosyl-L-methionine + demethylphylloquinol = S-adenosyl-L-homocysteine + phylloquinol
Glossary: demethylphylloquinol = 2-phytyl-1,4-naphthoquinol
phylloquinol = 2-methyl-3-phytyl-1,4-naphthoquinol = vitamin K1
Other name(s): menG (gene name); 2-phytyl-1,4-naphthoquinol methyltransferase
Systematic name: S-adenosyl-L-methionine:2-phytyl-1,4-naphthoquinol C-methyltransferase
Comments: The enzyme, found in plants and cyanobacteria, catalyses the final step in the biosynthesis of phylloquinone (vitamin K1), an electron carrier associated with photosystem I. The enzyme is specific for the quinol form of the substrate, and does not act on the quinone form [3].
References:
1.  Sakuragi, Y., Zybailov, B., Shen, G., Jones, A.D., Chitnis, P.R., van der Est, A., Bittl, R., Zech, S., Stehlik, D., Golbeck, J.H. and Bryant, D.A. Insertional inactivation of the menG gene, encoding 2-phytyl-1,4-naphthoquinone methyltransferase of Synechocystis sp. PCC 6803, results in the incorporation of 2-phytyl-1,4-naphthoquinone into the A1 site and alteration of the equilibrium constant between A1 and F(X) in photosystem I. Biochemistry 41 (2002) 394–405. [PMID: 11772039]
2.  Lohmann, A., Schottler, M.A., Brehelin, C., Kessler, F., Bock, R., Cahoon, E.B. and Dormann, P. Deficiency in phylloquinone (vitamin K1) methylation affects prenyl quinone distribution, photosystem I abundance, and anthocyanin accumulation in the Arabidopsis AtmenG mutant. J. Biol. Chem. 281 (2006) 40461–40472. [PMID: 17082184]
3.  Fatihi, A., Latimer, S., Schmollinger, S., Block, A., Dussault, P.H., Vermaas, W.F., Merchant, S.S. and Basset, G.J. A dedicated type II NADPH dehydrogenase performs the penultimate step in the biosynthesis of vitamin K1 in Synechocystis and Arabidopsis. Plant Cell 27 (2015) 1730–1741. [PMID: 26023160]
[EC 2.1.1.329 created 2016]
 
 
EC 2.1.1.330     
Accepted name: 5′-demethylyatein 5′-O-methyltransferase
Reaction: S-adenosyl-L-methionine + (–)-5′-demethylyatein = S-adenosyl-L-homocysteine + (–)-yatein
Glossary: (–)-5′-demethylyatein = (3R,4R)-4-(2,3-benzodioxol-5-ylmethyl)-3-(3-hydroxy-4,5-dimethoxybenzyl)dihydrofuran-2(3H)-one
(–)-yatein = (3R,4R)-4-(1,3-benzodioxol-5-ylmethyl)-3-(3,4,5-trimethoxybenzyl)dihydrofuran-2(3H)-one
Other name(s): OMT1 (gene name)
Systematic name: S-adenosyl-L-methionine:(–)-5′-demethylyatein 5′-O-methyltransferase
Comments: The enzyme, characterized from the plant Sinopodophyllum hexandrum, is involved in the biosynthetic pathway of podophyllotoxin, a non-alkaloid toxin lignan whose derivatives are important anticancer drugs.
References:
1.  Lau, W. and Sattely, E.S. Six enzymes from mayapple that complete the biosynthetic pathway to the etoposide aglycone. Science 349 (2015) 1224–1228. [PMID: 26359402]
[EC 2.1.1.330 created 2016]
 
 
EC 2.1.1.331     
Accepted name: bacteriochlorophyllide d C-121-methyltransferase
Reaction: S-adenosyl-L-methionine + 8-ethyl-12-methyl-3-vinylbacteriochlorophyllide d = S-adenosyl-L-homocysteine + 8,12-diethyl-3-vinylbacteriochlorophyllide d
Other name(s): bchR (gene name)
Systematic name: S-adenosyl-L-methionine:8-ethyl-12-methyl-3-vinylbacteriochlorophyllide-d C-121-methyltransferase
Comments: This enzyme, found in green sulfur bacteria (Chlorobiaceae) and green flimentous bacteria (Chloroflexaceae), is a radical S-adenosyl-L-methionine (AdoMet) enzyme and contains a [4Fe-4S] cluster. It adds a methyl group at the C-121 position of bacteriochlorophylls of the c, d and e types. This methylation plays a role in fine-tuning the structural arrangement of the bacteriochlorophyll aggregates in chlorosomes and therefore directly influences the chlorosomes absorption properties.
References:
1.  Gomez Maqueo Chew, A., Frigaard, N.U. and Bryant, D.A. Bacteriochlorophyllide c C-82 and C-121 methyltransferases are essential for adaptation to low light in Chlorobaculum tepidum. J. Bacteriol. 189 (2007) 6176–6184. [PMID: 17586634]
[EC 2.1.1.331 created 2016]
 
 
EC 2.1.1.332     
Accepted name: bacteriochlorophyllide d C-82-methyltransferase
Reaction: (1) S-adenosyl-L-methionine + 8,12-diethyl-3-vinylbacteriochlorophyllide d = S-adenosyl-L-homocysteine + 12-ethyl-8-propyl-3-vinylbacteriochlorophyllide d
(2) S-adenosyl-L-methionine + 12-ethyl-8-propyl-3-vinylbacteriochlorophyllide d = S-adenosyl-L-homocysteine + 12-ethyl-8-isobutyl-3-vinylbacteriochlorophyllide d
Other name(s): bchQ (gene name)
Systematic name: S-adenosyl-L-methionine:8,12-diethyl-3-vinylbacteriochlorophyllide-d C-82-methyltransferase
Comments: This enzyme, found in green sulfur bacteria (Chlorobiaceae) and green flimentous bacteria (Chloroflexaceae), is a radical S-adenosyl-L-methionine (AdoMet) enzyme and contains a [4Fe-4S] cluster. It adds one or two methyl groups at the C-82 position of bacteriochlorophylls of the c, d and e types. These methylations play a role in fine-tuning the structural arrangement of the bacteriochlorophyll aggregates in chlorosomes and therefore directly influence chlorosomal absorption properties.
References:
1.  Gomez Maqueo Chew, A., Frigaard, N.U. and Bryant, D.A. Bacteriochlorophyllide c C-82 and C-121 methyltransferases are essential for adaptation to low light in Chlorobaculum tepidum. J. Bacteriol. 189 (2007) 6176–6184. [PMID: 17586634]
[EC 2.1.1.332 created 2016]
 
 
EC 2.1.1.333     
Accepted name: bacteriochlorophyllide d C-20 methyltransferase
Reaction: S-adenosyl-L-methionine + a bacteriochlorophyllide d = S-adenosyl-L-homocysteine + a bacteriochlorophyllide c
Other name(s): bchU (gene name)
Systematic name: S-adenosyl-L-methionine:bacteriochlorophyllide-d C-20 methyltransferase
Comments: The enzyme, found in green sulfur bacteria (Chlorobiaceae) and green flimentous bacteria (Chloroflexaceae), catalyses the methylation of the C-20 methine bridge position in bacteriochlorophyllide d, forming bacteriochlorophyllide c.
References:
1.  Maresca, J.A., Gomez Maqueo Chew, A., Ponsati, M.R., Frigaard, N.U., Ormerod, J.G. and Bryant, D.A. The bchU gene of Chlorobium tepidum encodes the c-20 methyltransferase in bacteriochlorophyll c biosynthesis. J. Bacteriol. 186 (2004) 2558–2566. [PMID: 15090495]
[EC 2.1.1.333 created 2016]
 
 
EC 2.1.1.334     
Accepted name: methanethiol S-methyltransferase
Reaction: S-adenosyl-L-methionine + methanethiol = S-adenosyl-L-homocysteine + dimethyl sulfide
Other name(s): mddA (gene name)
Systematic name: S-adenosyl-L-methionine:methanethiol S-methyltransferase
Comments: The enzyme, found in many bacterial taxa, is involved in a pathway that converts L-methionine to dimethyl sulfide.
References:
1.  Carrion, O., Curson, A.R., Kumaresan, D., Fu, Y., Lang, A.S., Mercade, E. and Todd, J.D. A novel pathway producing dimethylsulphide in bacteria is widespread in soil environments. Nat. Commun. 6:6579 (2015). [PMID: 25807229]
[EC 2.1.1.334 created 2016]
 
 
EC 2.1.1.335     
Accepted name: 4-amino-anhydrotetracycline N4-methyltransferase
Reaction: (1) S-adenosyl-L-methionine + 4-amino-4-de(dimethylamino)anhydrotetracycline = S-adenosyl-L-homocysteine + 4-methylamino-4-de(dimethylamino)anhydrotetracycline
(2) S-adenosyl-L-methionine + 4-methylamino-4-de(dimethylamino)anhydrotetracycline = S-adenosyl-L-homocysteine + anhydrotetracycline
Glossary: 4-amino-4-de(dimethylamino)anhydrotetracycline = (4S,4aS,12aS)-4-amino-3,10,11,12a-tetrahydroxy-6-methyl-1,12-dioxo-4a,5-dihydro-4H-tetracene-2-carboxamide
4-methylamino-4-de(dimethylamino)anhydrotetracycline = (4S,4aS,12aS)-3,10,11,12a-tetrahydroxy-6-methyl-4-(methylamino)-1,12-dioxo-4a,5-dihydro-4H-tetracene-2-carboxamide
anhydrotetracycline = (4S,4aS,12aS)-4-(dimethylamino)-3,10,11,12a-tetrahydroxy-6-methyl-1,12-dioxo-1,4,4a,5,12,12a-hexahydrotetracene-2-carboxamide
Other name(s): oxyT (gene name); ctcO (gene name)
Systematic name: S-adenosyl-L-methionine:(4S,4aS,12aS)-4-amino-3,10,11,12a-tetrahydroxy-6-methyl-1,12-dioxo-4a,5-dihydro-4H-tetracene-2-carboxamide Nα-methyltransferase
Comments: The enzyme, characterized from the bacterium Streptomyces rimosus, participates in the biosynthesis of tetracycline antibiotics.
References:
1.  Zhang, W., Watanabe, K., Cai, X., Jung, M.E., Tang, Y. and Zhan, J. Identifying the minimal enzymes required for anhydrotetracycline biosynthesis. J. Am. Chem. Soc. 130 (2008) 6068–6069. [PMID: 18422316]
[EC 2.1.1.335 created 2016]
 
 
EC 2.1.1.336     
Accepted name: norbelladine O-methyltransferase
Reaction: S-adenosyl-L-methionine + norbelladine = S-adenosyl-L-homocysteine + 4′-O-methylnorbelladine
Glossary: norbelladine = 4-({[2-(4-hydroxyphenyl)ethyl]amino}methyl)benzene-1,2-diol
4′-O-methylnorbelladine = 5-({[2-(4-hydroxyphenyl)ethyl]amino}methyl)-2-methoxyphenol
Other name(s): N4OMT1 (gene name)
Systematic name: S-adenosyl-L-methionine:norbelladine O-methyltransferase
Comments: The enzyme, characterized from the plants Nerine bowdenii and Narcissus pseudonarcissus (daffodil), participates in the biosynthesis of alkaloids produced by plants that belong to the Amaryllidaceae family.
References:
1.  Mann, J.D., Fales, H.M. and Mudd, S.H. Alkaloids and plant metabolism. VI. O-methylation in vitro of norbelladine, a precursor of Amaryllidaceae alkaloids. J. Biol. Chem. 238 (1963) 3820–3823. [PMID: 14109227]
2.  Kilgore, M.B., Augustin, M.M., Starks, C.M., O'Neil-Johnson, M., May, G.D., Crow, J.A. and Kutchan, T.M. Cloning and characterization of a norbelladine 4′-O-methyltransferase involved in the biosynthesis of the Alzheimer’s drug galanthamine in Narcissus sp. aff. pseudonarcissus. PLoS One 9:e103223 (2014). [PMID: 25061748]
[EC 2.1.1.336 created 2016]
 
 
EC 2.1.1.337     
Accepted name: reticuline N-methyltransferase
Reaction: (1) S-adenosyl-L-methionine + (S)-reticuline = S-adenosyl-L-homocysteine + (S)-tembetarine
(2) S-adenosyl-L-methionine + (S)-corytuberine = S-adenosyl-L-homocysteine + (S)-magnoflorine
Glossary: (S)-reticuline = (1S)-1-(3-hydroxy-4-methoxybenzyl)-6-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ol
(S)-tembetarine = (1S)-1-(3-hydroxy-4-methoxybenzyl)-6-methoxy-2,2-dimethyl-1,2,3,4-tetrahydroisoquinolin-7-ol
(S)-corytuberine = (6aS)-2,10-dimethoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-1,11-diol
(S)-magnoflorine = (6aS)-1,11-dihydroxy-2,10-dimethoxy-6,6-dimethyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolinium
Other name(s): RNMT
Systematic name: S-adenosyl-L-methionine:(S)-reticuline N-methyltransferase
Comments: The enzyme from opium poppy (Papaver somniferum) can also methylate (R)-reticuline, tetrahydropapaverine, (S)-glaucine and (S)-bulbocapnine. It is involved in the biosynthesis of the quaternary benzylisoquinoline alkaloid magnoflorine.
References:
1.  Morris, J.S. and Facchini, P.J. Isolation and characterization of reticuline N-methyltransferase involved in biosynthesis of the aporphine alkaloid magnoflorine in opium poppy. J. Biol. Chem. 291 (2016) 23416–23427. [PMID: 27634038]
[EC 2.1.1.337 created 2017]
 
 
EC 2.1.1.338     
Accepted name: desmethylxanthohumol 6′-O-methyltransferase
Reaction: S-adenosyl-L-methionine + desmethylxanthohumol = S-adenosyl-L-homocysteine + xanthohumol
Glossary: desmethylxanthohumol = 2′,4,4′,6′-tetrahydroxy-3-prenylchalcone = (2E)-3-(4-hydroxyphenyl)-1-[2,4,6-trihydroxy-3-(3-methylbut-2-en-1-yl)phenyl]prop-2-en-1-one
xanthohumol = 2′,4,4′-trihydroxy-6′-methoxy-3-prenylchalcone = (2E)-1-[2,4-dihydroxy-6-methoxy-3-(3-methylbut-2-en-1-yl)phenyl]-3-(4-hydroxyphenyl)prop-2-en-1-one
Other name(s): OMT1 (ambiguous)
Systematic name: S-adenosyl-L-methionine:desmethylxanthohumol 6′-O-methyltransferase
Comments: Found in hops (Humulus lupulus). The enzyme can also methylate xanthogalenol.
References:
1.  Nagel, J., Culley, L.K., Lu, Y., Liu, E., Matthews, P.D., Stevens, J.F. and Page, J.E. EST analysis of hop glandular trichomes identifies an O-methyltransferase that catalyzes the biosynthesis of xanthohumol. Plant Cell 20 (2008) 186–200. [PMID: 18223037]
[EC 2.1.1.338 created 2017]
 
 
EC 2.1.1.339     
Accepted name: xanthohumol 4-O-methyltransferase
Reaction: S-adenosyl-L-methionine + xanthohumol = S-adenosyl-L-homocysteine + 4-O-methylxanthohumol
Glossary: xanthohumol = 2′,4,4′-trihydroxy-6′-methoxy-3-prenylchalcone = (2E)-1-[2,4-dihydroxy-6-methoxy-3-(3-methylbut-2-en-1-yl)phenyl]-3-(4-hydroxyphenyl)prop-2-en-1-one
4-O-methylxanthohumol =2′,4′-dihydroxy-4,6′-dimethoxy-3-prenylchalcone = (2E)-1-[2,4-dihydroxy-6-methoxy-3-(3-methylbut-2-en-1-yl)phenyl]-3-(4-methoxyphenyl)prop-2-en-1-one
Other name(s): OMT2 (ambiguous); S-adenosyl-L-methionine:xanthohumol 4′-O-methyltransferase (incorrect); xanthohumol 4′-O-methyltransferase (incorrect)
Systematic name: S-adenosyl-L-methionine:xanthohumol 4-O-methyltransferase
Comments: The enzyme from hops (Humulus lupulus) has a broad substrate specificity. The best substrates in vitro are resveratrol, desmethylxanthohumol, naringenin chalcone and isoliquiritigenin.
References:
1.  Nagel, J., Culley, L.K., Lu, Y., Liu, E., Matthews, P.D., Stevens, J.F. and Page, J.E. EST analysis of hop glandular trichomes identifies an O-methyltransferase that catalyzes the biosynthesis of xanthohumol. Plant Cell 20 (2008) 186–200. [PMID: 18223037]
[EC 2.1.1.339 created 2017, modified 2018]
 
 
EC 2.1.1.340     
Accepted name: 3-aminomethylindole N-methyltransferase
Reaction: 2 S-adenosyl-L-methionine + 3-(aminomethyl)indole = 2 S-adenosyl-L-homocysteine + gramine (overall reaction)
(1a) S-adenosyl-L-methionine + 3-(aminomethyl)indole = S-adenosyl-L-homocysteine + (1H-indol-3-yl)-N-methylmethanamine
(1b) S-adenosyl-L-methionine + (1H-indol-3-yl)-N-methylmethanamine = S-adenosyl-L-homocysteine + gramine
Glossary: 3-(aminomethyl)indole = (1H-indol-3-yl)methanamine
gramine = (1H-indol-3-ylmethyl)dimethylamine = (1H-indol-3-yl)-N,N-dimethylmethanamine
Other name(s): NMT (gene name)
Systematic name: S-adenosyl-L-methionine:3-(aminomethyl)indole N-methyltransferase (gramine-forming)
Comments: The enzyme, characterized from Hordeum vulgare (barley), catalyses two successive N-methylation reactions during the biosynthesis of gramine, a toxic indole alkaloid.
References:
1.  Leland, T.J. and Hanson, A.D. Induction of a specific N-methyltransferase enzyme by long-term heat stress during barley leaf growth. Plant Physiol. 79 (1985) 451–457. [PMID: 16664431]
2.  Larsson, K.A., Zetterlund, I., Delp, G. and Jonsson, L.M. N-Methyltransferase involved in gramine biosynthesis in barley: cloning and characterization. Phytochemistry 67 (2006) 2002–2008. [PMID: 16930646]
[EC 2.1.1.340 created 2017]
 
 
EC 2.1.1.341     
Accepted name: vanillate/3-O-methylgallate O-demethylase
Reaction: (1) vanillate + tetrahydrofolate = protocatechuate + 5-methyltetrahydrofolate
(2) 3-O-methylgallate + tetrahydrofolate = gallate + 5-methyltetrahydrofolate
Glossary: protocatechuate = 3,4-dihydroxybenzoate
vanillate = 4-hydroxy-3-methoxybenzoate
gallate = 3,4,5-trihydroxybenzoate
Other name(s): ligM (gene name)
Systematic name: vanillate:tetrahydrofolate O-methyltransferase
Comments: The enzyme, characterized from the bacterium Sphingomonas sp. SYK6, is involved in the degradation of lignin. The enzyme has similar activities with vanillate and 3-O-methylgallate.
References:
1.  Nishikawa, S., Sonoki, T., Kasahara, T., Obi, T., Kubota, S., Kawai, S., Morohoshi, N. and Katayama, Y. Cloning and sequencing of the Sphingomonas (Pseudomonas) paucimobilis gene essential for the O demethylation of vanillate and syringate. Appl. Environ. Microbiol. 64 (1998) 836–842. [PMID: 9501423]
2.  Masai, E., Sasaki, M., Minakawa, Y., Abe, T., Sonoki, T., Miyauchi, K., Katayama, Y. and Fukuda, M. A novel tetrahydrofolate-dependent O-demethylase gene is essential for growth of Sphingomonas paucimobilis SYK-6 with syringate. J. Bacteriol. 186 (2004) 2757–2765. [PMID: 15090517]
3.  Abe, T., Masai, E., Miyauchi, K., Katayama, Y. and Fukuda, M. A tetrahydrofolate-dependent O-demethylase, LigM, is crucial for catabolism of vanillate and syringate in Sphingomonas paucimobilis SYK-6. J. Bacteriol. 187 (2005) 2030–2037. [PMID: 15743951]
[EC 2.1.1.341 created 2017]
 
 
EC 2.1.1.342     
Accepted name: anaerobilin synthase
Reaction: 2 S-adenosyl-L-methionine + protoheme + 2 reduced flavodoxin = S-adenosyl-L-homocysteine + L-methionine + 5′-deoxyadenosine + anaerobilin + Fe2+ + 2 oxidized flavodoxin
Glossary: anaerobilin = (4Z,10Z,14E)-8,12-bis(2-carboxyethyl)-3,7,13,18-tetramethyl-1,2,17-trivinyl-23,24-dihydrobilin
Other name(s): chuW (gene name)
Systematic name: S-adenosyl-L-methionine:protoheme C-methyltransferase (anaerobilin-producing)
Comments: The enzyme, studied from the bacterium Escherichia coli O157:H7, is a radical SAM (AdoMet) enzyme that is involved in heme degradation and iron utilization under anaerobic conditions. The enzyme uses two SAM molecules for the reaction. The first molecule is used to generate a 5′-deoxyadenosyl radical, which abstracts a hydrogen atom from the methyl group of the second SAM molecule. The newly formed methylene radical attacks the substrate, causing a rearrangement of the porphyrin ring that results in the liberation of iron.
References:
1.  LaMattina, J.W., Nix, D.B. and Lanzilotta, W.N. Radical new paradigm for heme degradation in Escherichia coli O157:H7. Proc. Natl. Acad. Sci. USA 113 (2016) 12138–12143. [PMID: 27791000]
2.  LaMattina, J.W., Delrossi, M., Uy, K.G., Keul, N.D., Nix, D.B., Neelam, A.R. and Lanzilotta, W.N. Anaerobic heme degradation: ChuY Is an anaerobilin reductase that exhibits kinetic cooperativity. Biochemistry 56 (2017) 845–855. [PMID: 28045510]
[EC 2.1.1.342 created 2017]
 
 
EC 2.1.1.343     
Accepted name: 8-amino-8-demethylriboflavin N,N-dimethyltransferase
Reaction: 2 S-adenosyl-L-methionine + 8-amino-8-demethylriboflavin = 2 S-adenosyl-L-homocysteine + roseoflavin (overall reaction)
(1a) S-adenosyl-L-methionine + 8-amino-8-demethylriboflavin = S-adenosyl-L-homocysteine + 8-demethyl-8-(methylamino)riboflavin
(1b) S-adenosyl-L-methionine + 8-demethyl-8-(methylamino)riboflavin = S-adenosyl-L-homocysteine + roseoflavin
Glossary: roseoflavin = 8-demethyl-8-(dimethylamino)riboflavin
Other name(s): rosA (gene name)
Systematic name: S-adenosyl-L-methionine:8-amino-8-demethylriboflavin N,N-dimethyltransferase
Comments: The enzyme, characterized from the soil bacterium Streptomyces davawensis, catalyses the last two steps in the biosynthesis of the antibiotic roseoflavin.
References:
1.  Jankowitsch, F., Kuhm, C., Kellner, R., Kalinowski, J., Pelzer, S., Macheroux, P. and Mack, M. A novel N,N-8-amino-8-demethyl-D-riboflavin dimethyltransferase (RosA) catalyzing the two terminal steps of roseoflavin biosynthesis in Streptomyces davawensis. J. Biol. Chem. 286 (2011) 38275–38285. [PMID: 21911488]
2.  Tongsook, C., Uhl, M.K., Jankowitsch, F., Mack, M., Gruber, K. and Macheroux, P. Structural and kinetic studies on RosA, the enzyme catalysing the methylation of 8-demethyl-8-amino-D-riboflavin to the antibiotic roseoflavin. FEBS J. 283 (2016) 1531–1549. [PMID: 26913589]
[EC 2.1.1.343 created 2017]
 
 
EC 2.1.1.344     
Accepted name: ornithine lipid N-methyltransferase
Reaction: 3 S-adenosyl-L-methionine + an ornithine lipid = 3 S-adenosyl-L-homocysteine + an N,N,N-trimethylornithine lipid (overall reaction)
(1a) S-adenosyl-L-methionine + an ornithine lipid = S-adenosyl-L-homocysteine + an N-methylornithine lipid
(1b) S-adenosyl-L-methionine + an N-methylornithine lipid = S-adenosyl-L-homocysteine + an N,N-dimethylornithine lipid
(1c) S-adenosyl-L-methionine + an N,N-dimethylornithine lipid = S-adenosyl-L-homocysteine + an N,N,N-trimethylornithine lipid
Glossary: an ornithine lipid = an Nα-[(3R)-3-(acyloxy)acyl]-L-ornithine
Other name(s): olsG (gene name)
Systematic name: S-adenosyl-L-methionine:ornithine lipid N-methyltransferase
Comments: The enzyme, characterized from the bacterium Singulisphaera acidiphila, catalyses three successive methylations of the terminal δ-nitrogen in ornithine lipids.
References:
1.  Escobedo-Hinojosa, W.I., Vences-Guzman, M.A., Schubotz, F., Sandoval-Calderon, M., Summons, R.E., Lopez-Lara, I.M., Geiger, O. and Sohlenkamp, C. OlsG (Sinac_1600) is an ornithine lipid N-methyltransferase from the planctomycete Singulisphaera acidiphila. J. Biol. Chem. 290 (2015) 15102–15111. [PMID: 25925947]
[EC 2.1.1.344 created 2017]
 
 
EC 2.1.1.345     
Accepted name: psilocybin synthase
Reaction: 2 S-adenosyl-L-methionine + 4-hydroxytryptamine 4-phosphate = 2 S-adenosyl-L-homocysteine + psilocybin (overall reaction)
(1a) S-adenosyl-L-methionine + 4-hydroxytryptamine 4-phosphate = S-adenosyl-L-homocysteine + 4-hydroxy-N-methyltryptamine 4-phosphate
(1b) S-adenosyl-L-methionine + 4-hydroxy-N-methyltryptamine 4-phosphate = S-adenosyl-L-homocysteine + psilocybin
Glossary: psilocybin = 3-[2-(dimethylamino)ethyl]-1H-indol-4-yl phosphate
Other name(s): PsiM
Systematic name: S-adenosyl-L-methionine:4-hydroxytryptamine-4-phosphate N,N-dimethyltransferase
Comments: Isolated from the fungus Psilocybe cubensis. The product, psilocybin, is a psychoactive compound.
References:
1.  Fricke, J., Blei, F. and Hoffmeister, D. Enzymatic synthesis of psilocybin. Angew. Chem. Int. Ed. Engl. 56 (2017) 12352–12355. [PMID: 28763571]
[EC 2.1.1.345 created 2017]
 
 
EC 2.1.1.346     
Accepted name: U6 snRNA m6A methyltransferase
Reaction: S-adenosyl-L-methionine + adenine in U6 snRNA = S-adenosyl-L-homocysteine + N6-methyladenine in U6 snRNA
Other name(s): METTL16 (gene name)
Systematic name: S-adenosyl-L-methionine:adenine in U6 snRNA methyltransferase
Comments: This enzyme, found in vertebrates, methylates a specific adenine in a hairpin structure of snRNA. The effects of the binding of the methyltransferase to its substrate is important for the regulation of the activity of an isoform of EC 2.5.1.6, methionine adenosyltransferase, that produces S-adenosyl-L-methionine [1,2]. The enzyme also binds (and maybe methylates) the lncRNAs XIST and MALAT1 as well as a number of pre-mRNAs at specific positions often found in the intronic regions [2].
References:
1.  Pendleton, K.E., Chen, B., Liu, K., Hunter, O.V., Xie, Y., Tu, B.P. and Conrad, N.K. The U6 snRNA m6A methyltransferase METTL16 regulates SAM synthetase intron retention. Cell 169 (2017) 824–835.e14. [PMID: 28525753]
2.  Warda, A.S., Kretschmer, J., Hackert, P., Lenz, C., Urlaub, H., Hobartner, C., Sloan, K.E. and Bohnsack, M.T. Human METTL16 is a N6-methyladenosine (m6A) methyltransferase that targets pre-mRNAs and various non-coding RNAs. EMBO Rep. 18 (2017) 2004–2014. [PMID: 29051200]
[EC 2.1.1.346 created 2018]
 
 
EC 2.1.1.347     
Accepted name: (+)-O-methylkolavelool synthase
Reaction: S-adenosyl-L-methionine + (+)-kolavelool = S-adenosyl-L-homocysteine + (+)-O-methylkolavelool
Other name(s): Haur_2147 (locus name)
Systematic name: S-adenosyl-L-methionine:(+)-kolavelool O-methyltransferase
Comments: Isolated from the bacterium Herpetosiphon aurantiacus.
References:
1.  Nakano, C., Oshima, M., Kurashima, N. and Hoshino, T. Identification of a new diterpene biosynthetic gene cluster that produces O-methylkolavelool in Herpetosiphon aurantiacus. ChemBioChem 16 (2015) 772–781. [PMID: 25694050]
[EC 2.1.1.347 created 2018]
 
 
EC 2.1.1.348     
Accepted name: mRNA m6A methyltransferase
Reaction: S-adenosyl-L-methionine + adenine in mRNA = S-adenosyl-L-homocysteine + N6-methyladenine in mRNA
Other name(s): METTL3 (gene name); METTL14 (gene name)
Systematic name: S-adenosyl-L-methionine:adenine in mRNA methyltransferase
Comments: This enzyme, found in eukaryotes, methylates adenines in mRNA with the consensus sequence RRACH.
References:
1.  Liu, J., Yue, Y., Han, D., Wang, X., Fu, Y., Zhang, L., Jia, G., Yu, M., Lu, Z., Deng, X., Dai, Q., Chen, W. and He, C. A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat. Chem. Biol. 10 (2014) 93–95. [PMID: 24316715]
2.  Wang, X., Huang, J., Zou, T. and Yin, P. Human m6A writers: Two subunits, 2 roles. RNA Biol. 14 (2017) 300–304. [PMID: 28121234]
[EC 2.1.1.348 created 2018]
 
 
EC 2.1.1.349     
Accepted name: toxoflavin synthase
Reaction: (1) S-adenosyl-L-methionine + 1,6-didemethyltoxoflavin = S-adenosyl-L-homocysteine + reumycin
(2) S-adenosyl-L-methionine + reumycin = S-adenosyl-L-homocysteine + toxoflavin
Glossary: reumycin = 1-demethyltoxoflavin
toxoflavin = 1,6-dimethylpyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione
Other name(s): toxA (gene name)
Systematic name: S-adenosyl-L-methionine:1,6-didemethyltoxoflavin N1,N6-dimethyltransferase (toxoflavin-forming)
Comments: The enzyme is a dual-specificity methyltransferase that catalyses the last two steps of toxoflavin biosynthesis. Toxoflavin is a major virulence factor of several bacterial crop pathogens.
References:
1.  Fenwick, M.K., Philmus, B., Begley, T.P. and Ealick, S.E. Burkholderia glumae ToxA Is a dual-specificity methyltransferase that catalyzes the last two steps of toxoflavin biosynthesis. Biochemistry 55 (2016) 2748–2759. [PMID: 27070241]
[EC 2.1.1.349 created 2018]
 
 
EC 2.1.1.350     
Accepted name: menaquinone C8-methyltransferase
Reaction: (1) 2 S-adenosyl-L-methionine + a menaquinone + reduced flavodoxin = S-adenosyl-L-homocysteine + L-methionine + 5′-deoxyadenosine + an 8-methylmenaquinone + oxidized flavodoxin
(2) 2 S-adenosyl-L-methionine + a 2-demethylmenaquinone + reduced flavodoxin = S-adenosyl-L-homocysteine + L-methionine + 5′-deoxyadenosine + a 2-demethyl-8-methylmenaquinone + oxidized flavodoxin
Other name(s): mqnK (gene name); menK (gene name)
Systematic name: S-adenosyl-L-methionine:menaquinone C8-methyltransferase
Comments: The enzyme, found in a wide range of bacteria and archaea, is a radical SAM (AdoMet) enzyme that utilizes two molecules of S-adenosyl-L-methionine, one as the methyl group donor, and one for the creation of a 5′-deoxyadenosine radical that drives the reaction forward.
References:
1.  Hein, S., Klimmek, O., Polly, M., Kern, M. and Simon, J. A class C radical S-adenosylmethionine methyltransferase synthesizes 8-methylmenaquinone. Mol. Microbiol. 104 (2017) 449–462. [PMID: 28164386]
[EC 2.1.1.350 created 2018]
 
 
EC 2.1.1.351     
Accepted name: nocamycin O-methyltransferase
Reaction: S-adenosyl-L-methionine + nocamycin E = S-adenosyl-L-homocysteine + nocamycin I
Glossary: nocamycin E = (2R,3S,3aS,5R,6R,7S,9aS)-5-[(2R,3E,5E)-7-hydroxy-4-methyl-7-(2,4-dioxopyrroliden-3-ylidene)hepta-3,5-dien-2-yl]-2,6,9a-trimethyl-8-oxooctahydro-3a,7-epoxyfuro[3,2-b]oxocine-3-carboxylate
nocamycin I = methyl (2R,3S,3aS,5R,6R,7S,9aS)-5-[(2R,3E,5E)-7-hydroxy-4-methyl-7-(2,4-dioxopyrroliden-3-ylidene)hepta-3,5-dien-2-yl]-2,6,9a-trimethyl-8-oxooctahydro-3a,7-epoxyfuro[3,2-b]oxocine-3-carboxylate
Other name(s): ncmP (gene name)
Systematic name: S-adenosyl-L-methionine:nocamycin E O-methyltransferase
Comments: The enzyme, isolated from the bacterium Saccharothrix syringae, is involved in the biosynthesis of nocamycin I and nocamycin II.
References:
1.  Mo, X., Gui, C. and Wang, Q. Elucidation of a carboxylate O-methyltransferase NcmP in nocamycin biosynthetic pathway. Bioorg. Med. Chem. Lett. 27 (2017) 4431–4435. [PMID: 28818448]
[EC 2.1.1.351 created 2018]
 
 
EC 2.1.1.352     
Accepted name: 3-O-acetyl-4′-O-demethylpapaveroxine 4′-O-methyltransferase
Reaction: S-adenosyl-L-methionine + 3-O-acetyl-4′-O-demethylpapaveroxine = S-adenosyl-L-homocysteine + 3-O-acetylpapaveroxine
Glossary: 3-O-acetyl-4′-O-demethylpapaveroxine = 6-{(S)-acetoxy[(5R)-4-hydroxy-6-methyl-5,6,7,8-tetrahydro[1,3]dioxolo[4,5-g]isoquinolin-5-yl]methyl}-2,3-dimethoxybenzaldehyde
3-O-acetylpapaveroxine = 6-{(S)-acetoxy[(5R)-4-methoxy-6-methyl-5,6,7,8-tetrahydro[1,3]dioxolo[4,5-g]isoquinolin-5-yl]methyl}-2,3-dimethoxybenzaldehyde
Systematic name: S-adenosyl-L-methionine:3-O-acetyl-4′-O-demethylpapaveroxine 4′-O-methyltransferase
Comments: This activity is part of the noscapine biosynthesis pathway, as characterized in the plant Papaver somniferum (opium poppy). It is catalysed by heterodimeric complexes of the OMT2 gene product and the product of either OMT3 or 6OMT. OMT2 is the catalytic subunit in both complexes.
References:
1.  Li, Y. and Smolke, C.D. Engineering biosynthesis of the anticancer alkaloid noscapine in yeast. Nat. Commun. 7:12137 (2016). [PMID: 27378283]
2.  Park, M.R., Chen, X., Lang, D.E., Ng, K.KS. and Facchini, P.J. Heterodimeric O-methyltransferases involved in the biosynthesis of noscapine in opium poppy. Plant J. 95 (2018) 252–267. [PMID: 29723437]
[EC 2.1.1.352 created 2018]
 
 
EC 2.1.1.353     
Accepted name: demethylluteothin O-methyltransferase
Reaction: S-adenosyl-L-methionine + demethylluteothin = S-adenosyl-L-homocysteine + luteothin
Glossary: luteothin = 2-[(3E,5E)-3,5-dimethyl-6-(4-nitrophenyl)hexa-3,5-dien-1-yl]-6-methoxy-3,5-dimethyl-4H-pyran-4-one
aureothin = 2-methoxy-3,5-dimethyl-6-[(2R,4Z)-4-[(2E)-2-methyl-3-(4-nitrophenyl)prop-2-en-1-ylidene]oxolan-2-yl]-4H-pyran-4-one
spectinabilin = neoaureothin = 2-methoxy-3,5-dimethyl-6-[(2R,4Z)-4-[(2E,4E,6E)-2,4,6-trimethyl-7-(4-nitrophenyl)hepta-2,4,6-trien-1-ylidene]oxolan-2-yl]-4H-pyran-4-one
Other name(s): aurI (gene name)
Systematic name: S-adenosyl-L-methionine:demethylluteothin O-methyltransferase
Comments: The enzyme, characterized from the bacterium Streptomyces thioluteus, participates in the biosynthesis of the antibiotic aureothin. An orthologous enzyme in the bacteria Streptomyces orinoci and Streptomyces spectabilis catalyses a similar reaction in the biosynthesis of spectinabilin.
References:
1.  He, J., Muller, M. and Hertweck, C. Formation of the aureothin tetrahydrofuran ring by a bifunctional cytochrome P450 monooxygenase. J. Am. Chem. Soc. 126 (2004) 16742–16743. [PMID: 15612710]
2.  Muller, M., He, J. and Hertweck, C. Dissection of the late steps in aureothin biosynthesis. ChemBioChem 7 (2006) 37–39. [PMID: 16292785]
[EC 2.1.1.353 created 2019]
 
 
EC 2.1.1.354     
Accepted name: [histone H3]-lysine4 N-trimethyltransferase
Reaction: 3 S-adenosyl-L-methionine + a [histone H3]-L-lysine4 = 3 S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine4 (overall reaction)
(1a) S-adenosyl-L-methionine + a [histone H3]-L-lysine4 = S-adenosyl-L-homocysteine + a [histone H3]-N6-methyl-L-lysine4
(1b) S-adenosyl-L-methionine + a [histone H3]-N6-methyl-L-lysine4 = S-adenosyl-L-homocysteine + a [histone H3]-N6,N6-dimethyl-L-lysine4
(1c) S-adenosyl-L-methionine + a [histone H3]-N6,N6-dimethyl-L-lysine4 = S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine4
Other name(s): KMT2A (gene name); KMT2B (gene name); KMT2C (gene name); KMT2D (gene name); KMT2E (gene name); KMT2F (gene name); KMT2G (gene name); KMT2H (gene name); KMT3C (gene name); KMT3D (gene name); KMT3E (gene name); KMT7 (gene name); PRDM7 (gene name); PRDM9 (gene name); MLL1 (gene name); MLL2 (gene name); MLL3 (gene name); MLL4 (gene name); MLL5 (gene name); SETD1A (gene name); ASH1L (gene name); SMYD1 (gene name); SMYD2 (gene name); SMYD3 (gene name); SET7/9 (gene name)
Systematic name: S-adenosyl-L-methionine:[histone H3]-L-lysine4 N6-methyltransferase
Comments: This entry describes several enzymes that successively methylate the L-lysine4 residue of histone H3 (H3K4), ultimately generating a trimethylated form. These modifications influence the binding of chromatin-associated proteins. In most cases the trimethylation of this position is associated with gene activation. Unlike the other enzymes, KMT7 catalyses only monomethylation.
References:
1.  Nakamura, T., Mori, T., Tada, S., Krajewski, W., Rozovskaia, T., Wassell, R., Dubois, G., Mazo, A., Croce, C.M. and Canaani, E. ALL-1 is a histone methyltransferase that assembles a supercomplex of proteins involved in transcriptional regulation. Mol. Cell 10 (2002) 1119–1128. [PMID: 12453419]
2.  Xiao, B., Jing, C., Wilson, J.R., Walker, P.A., Vasisht, N., Kelly, G., Howell, S., Taylor, I.A., Blackburn, G.M. and Gamblin, S.J. Structure and catalytic mechanism of the human histone methyltransferase SET7/9. Nature 421 (2003) 652–656. [PMID: 12540855]
3.  Hamamoto, R., Furukawa, Y., Morita, M., Iimura, Y., Silva, F.P., Li, M., Yagyu, R. and Nakamura, Y. SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells. Nat. Cell Biol. 6 (2004) 731–740. [PMID: 15235609]
4.  Blazer, L.L., Lima-Fernandes, E., Gibson, E., Eram, M.S., Loppnau, P., Arrowsmith, C.H., Schapira, M. and Vedadi, M. PR domain-containing protein 7 (PRDM7) is a histone 3 lysine 4 trimethyltransferase. J. Biol. Chem. 291 (2016) 13509–13519. [PMID: 27129774]
[EC 2.1.1.354 created 1976 as EC 2.1.1.43, modified 1982, modified 1983, part transferred 2019 to EC 2.1.1.354]
 
 
EC 2.1.1.355     
Accepted name: [histone H3]-lysine9 N-trimethyltransferase
Reaction: 3 S-adenosyl-L-methionine + a [histone H3]-L-lysine9 = 3 S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine9 (overall reaction)
(1a) S-adenosyl-L-methionine + a [histone H3]-L-lysine9 = S-adenosyl-L-homocysteine + a [histone H3]-N6-methyl-L-lysine9
(1b) S-adenosyl-L-methionine + a [histone H3]-N6-methyl-L-lysine9 = S-adenosyl-L-homocysteine + a [histone H3]-N6,N6-dimethyl-L-lysine9
(1c) S-adenosyl-L-methionine + a [histone H3]-N6,N6-dimethyl-L-lysine9 = S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine9
Other name(s): KMT1A (gene name); KMT1B (gene name); KMT1C (gene name); KMT1D (gene name); KMT1E (gene name); KMT1F (gene name); MT8 (gene name); SUV39H1 (gene name); G9A (gene name); EHMT1 (gene name); PRDM2 (gene name)
Systematic name: S-adenosyl-L-methionine:[histone H3]-L-lysine9 N6-methyltransferase
Comments: This entry describes several enzymes that successively methylate the L-lysine9 residue of histone H3 (H3K9), ultimately generating a trimethylated form. These modifications influence the binding of chromatin-associated proteins. In general, the methylation of H3K9 leads to transcriptional repression of the affected target genes.
References:
1.  O'Carroll, D., Scherthan, H., Peters, A.H., Opravil, S., Haynes, A.R., Laible, G., Rea, S., Schmid, M., Lebersorger, A., Jerratsch, M., Sattler, L., Mattei, M.G., Denny, P., Brown, S.D., Schweizer, D. and Jenuwein, T. Isolation and characterization of Suv39h2, a second histone H3 methyltransferase gene that displays testis-specific expression. Mol. Cell Biol. 20 (2000) 9423–9433. [PMID: 11094092]
2.  Schotta, G., Ebert, A., Krauss, V., Fischer, A., Hoffmann, J., Rea, S., Jenuwein, T., Dorn, R. and Reuter, G. Central role of Drosophila SU(VAR)3-9 in histone H3-K9 methylation and heterochromatic gene silencing. EMBO J. 21 (2002) 1121–1131. [PMID: 11867540]
3.  Tachibana, M., Sugimoto, K., Nozaki, M., Ueda, J., Ohta, T., Ohki, M., Fukuda, M., Takeda, N., Niida, H., Kato, H. and Shinkai, Y. G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis. Genes Dev. 16 (2002) 1779–1791. [PMID: 12130538]
4.  Schultz, D.C., Ayyanathan, K., Negorev, D., Maul, G.G. and Rauscher, F.J., 3rd. SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins. Genes Dev. 16 (2002) 919–932. [PMID: 11959841]
5.  Kim, K.C., Geng, L. and Huang, S. Inactivation of a histone methyltransferase by mutations in human cancers. Cancer Res. 63 (2003) 7619–7623. [PMID: 14633678]
6.  Wu, H., Min, J., Lunin, V.V., Antoshenko, T., Dombrovski, L., Zeng, H., Allali-Hassani, A., Campagna-Slater, V., Vedadi, M., Arrowsmith, C.H., Plotnikov, A.N. and Schapira, M. Structural biology of human H3K9 methyltransferases. PLoS One 5:e8570 (2010). [PMID: 20084102]
[EC 2.1.1.355 created 1976 as EC 2.1.1.43, modified 1982, modified 1983, part transferred 2019 to EC 2.1.1.355]
 
 
EC 2.1.1.356     
Accepted name: [histone H3]-lysine27 N-trimethyltransferase
Reaction: 3 S-adenosyl-L-methionine + a [histone H3]-L-lysine27 = 3 S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine27 (overall reaction)
(1a) S-adenosyl-L-methionine + a [histone H3]-L-lysine27 = S-adenosyl-L-homocysteine + a [histone H3]-N6-methyl-L-lysine27
(1b) S-adenosyl-L-methionine + a [histone H3]-N6-methyl-L-lysine27 = S-adenosyl-L-homocysteine + a [histone H3]-N6,N6-dimethyl-L-lysine27
(1c) S-adenosyl-L-methionine + a [histone H3]-N6,N6-dimethyl-L-lysine27 = S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine27
Other name(s): KMT6A (gene name); KMT6B (gene name); EZH1 (gene name); EZH2 (gene name)
Systematic name: S-adenosyl-L-methionine:[histone H3]-L-lysine27 N6-methyltransferase
Comments: This entry describes enzymes that successively methylate the L-lysine27 residue of histone H3 (H3K27), ultimately generating a trimethylated form. These modifications influence the binding of chromatin-associated proteins. The methylation of lysine27 leads to transcriptional repression of the affected target genes. The enzyme associates with other proteins to form a complex that is essential for activity. The enzyme can also methylate some non-histone proteins.
References:
1.  Cao, R., Wang, L., Wang, H., Xia, L., Erdjument-Bromage, H., Tempst, P., Jones, R.S. and Zhang, Y. Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science 298 (2002) 1039–1043. [PMID: 12351676]
2.  Kuzmichev, A., Nishioka, K., Erdjument-Bromage, H., Tempst, P. and Reinberg, D. Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein. Genes Dev. 16 (2002) 2893–2905. [PMID: 12435631]
3.  Kirmizis, A., Bartley, S.M., Kuzmichev, A., Margueron, R., Reinberg, D., Green, R. and Farnham, P.J. Silencing of human polycomb target genes is associated with methylation of histone H3 Lys 27. Genes Dev. 18 (2004) 1592–1605. [PMID: 15231737]
4.  Schlesinger, Y., Straussman, R., Keshet, I., Farkash, S., Hecht, M., Zimmerman, J., Eden, E., Yakhini, Z., Ben-Shushan, E., Reubinoff, B.E., Bergman, Y., Simon, I. and Cedar, H. Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer. Nat. Genet. 39 (2007) 232–236. [PMID: 17200670]
5.  Shen, X., Liu, Y., Hsu, Y.J., Fujiwara, Y., Kim, J., Mao, X., Yuan, G.C. and Orkin, S.H. EZH1 mediates methylation on histone H3 lysine 27 and complements EZH2 in maintaining stem cell identity and executing pluripotency. Mol. Cell 32 (2008) 491–502. [PMID: 19026780]
6.  Ezhkova, E., Lien, W.H., Stokes, N., Pasolli, H.A., Silva, J.M. and Fuchs, E. EZH1 and EZH2 cogovern histone H3K27 trimethylation and are essential for hair follicle homeostasis and wound repair. Genes Dev. 25 (2011) 485–498. [PMID: 21317239]
[EC 2.1.1.356 created 1976 as EC 2.1.1.43, modified 1982, modified 1983, part transferred 2019 to EC 2.1.1.356]
 
 
EC 2.1.1.357     
Accepted name: [histone H3]-lysine36 N-dimethyltransferase
Reaction: 2 S-adenosyl-L-methionine + a [histone H3]-L-lysine36 = 2 S-adenosyl-L-homocysteine + a [histone H3]-N6,N6-dimethyl-L-lysine36 (overall reaction)
(1a) S-adenosyl-L-methionine + a [histone H3]-L-lysine36 = S-adenosyl-L-homocysteine + a [histone H3]-N6-methyl-L-lysine36
(1b) S-adenosyl-L-methionine + a [histone H3]-N6-methyl-L-lysine36 = S-adenosyl-L-homocysteine + a [histone H3]-N6,N6-dimethyl-L-lysine36
Other name(s): KMT3B (gene name); KMT3C (gene name); NSD2 (gene name); NSD3 (gene name); SETMAR (gene name); WHSC1 (gene name)
Systematic name: S-adenosyl-L-methionine:[histone H3]-L-lysine36 N6-dimethyltransferase
Comments: This entry describes a group of metazoan enzymes that catalyse two successive methylations of lysine36 of histone H3 (H3K36), forming mono- and dimethylated forms. These modifications influence the binding of chromatin-associated proteins. The product can be further methylated to the trimethyl form by EC 2.1.1.358, [histone H3]-dimethyl-L-lysine36 N-methyltransferase. The yeast SET2 enzyme can catalyse all three methylations (see EC 2.1.1.359, [histone H3]-lysine36 N-trimethyltransferase).
References:
1.  Fnu, S., Williamson, E.A., De Haro, L.P., Brenneman, M., Wray, J., Shaheen, M., Radhakrishnan, K., Lee, S.H., Nickoloff, J.A. and Hromas, R. Methylation of histone H3 lysine 36 enhances DNA repair by nonhomologous end-joining. Proc. Natl. Acad. Sci. USA 108 (2011) 540–545. [PMID: 21187428]
2.  Kuo, A.J., Cheung, P., Chen, K., Zee, B.M., Kioi, M., Lauring, J., Xi, Y., Park, B.H., Shi, X., Garcia, B.A., Li, W. and Gozani, O. NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic programming. Mol. Cell 44 (2011) 609–620. [PMID: 22099308]
3.  Qiao, Q., Li, Y., Chen, Z., Wang, M., Reinberg, D. and Xu, R.M. The structure of NSD1 reveals an autoregulatory mechanism underlying histone H3K36 methylation. J. Biol. Chem. 286 (2011) 8361–8368. [PMID: 21196496]
4.  Wagner, E.J. and Carpenter, P.B. Understanding the language of Lys36 methylation at histone H3. Nat. Rev. Mol. Cell. Biol. 13 (2012) 115–126. [PMID: 22266761]
[EC 2.1.1.357 created 1976 as EC 2.1.1.43, modified 1982, modified 1983, part transferred 2019 to EC 2.1.1.357]
 
 
EC 2.1.1.358     
Accepted name: [histone H3]-dimethyl-L-lysine36 N-methyltransferase
Reaction: S-adenosyl-L-methionine + a [histone H3]-N6,N6-dimethyl-L-lysine36 = S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine36
Other name(s): KMT3A (gene name); SETD2 (gene name)
Systematic name: S-adenosyl-L-methionine:[histone H3]-N6,N6-dimethyl-L-lysine36 N6-methyltransferase
Comments: The enzyme, found in metazoa, methylates a dimethylated L-lysine36 residue of histone H3 (H3K36), which has been methylated previously by EC 2.1.1.357, [histone H3]-lysine36 N-dimethyltransferase. The homologous enzyme from yeast catalyses all three methylations (see EC 2.1.1.359, [histone H3]-lysine36 N-trimethyltransferase).
References:
1.  Kizer, K.O., Phatnani, H.P., Shibata, Y., Hall, H., Greenleaf, A.L. and Strahl, B.D. A novel domain in Set2 mediates RNA polymerase II interaction and couples histone H3 K36 methylation with transcript elongation. Mol. Cell Biol. 25 (2005) 3305–3316. [PMID: 15798214]
2.  Yuan, W., Xie, J., Long, C., Erdjument-Bromage, H., Ding, X., Zheng, Y., Tempst, P., Chen, S., Zhu, B. and Reinberg, D. Heterogeneous nuclear ribonucleoprotein L Is a subunit of human KMT3a/Set2 complex required for H3 Lys-36 trimethylation activity in vivo. J. Biol. Chem. 284 (2009) 15701–15707. [PMID: 19332550]
3.  Wagner, E.J. and Carpenter, P.B. Understanding the language of Lys36 methylation at histone H3. Nat. Rev. Mol. Cell. Biol. 13 (2012) 115–126. [PMID: 22266761]
[EC 2.1.1.358 created 1976 as EC 2.1.1.43, modified 1982, modified 1983, part transferred 2019 to EC 2.1.1.358]