Reaction: 5-methyltetrahydrofolate + L-homocysteine = tetrahydrofolate + L-methionine
For diagram of reaction click here and mechanism click here.
Other name(s): 5-methyltetrahydrofolatehomocysteine S-methyltransferase; 5-methyltetrahydrofolatehomocysteine transmethylase; N-methyltetrahydrofolate:L-homocysteine methyltransferase; N5-methyltetrahydrofolate methyltransferase; N5-methyltetrahydrofolatehomocysteine cobalamin methyltransferase; N5-methyltetrahydrofolichomocysteine vitamin B12 transmethylase; B12 N5-methyltetrahydrofolate homocysteine methyltransferase; methyltetrahydrofolatehomocysteine 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 220.127.116.11, [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 18.104.22.168, ferredoxinNADP+ reductase). Acts on the monoglutamate as well as the triglutamate folate, in contrast with EC 22.214.171.124, 5-methyltetrahydropteroyltriglutamatehomocysteine S-methyltransferase, which acts only on the triglutamate.
Links to other databases: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number: 9033-23-2
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.
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.
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.
5. Taylor, R.T. Escherichia coli B N5-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]