IntEnz

EC 2.1.1.13 - Methionine synthase

IntEnz Enzyme Nomenclature
EC 2.1.1.13

Names

Reaction

• 11172 [IUBMB]
  (6S)-5-methyl-5,6,7,8-tetrahydrofolate

  (6S)-5-methyl-5,6,7,8-tetrahydrofolate

  Name origin: UniProt - CHECKED (C)

  CHEBI:18608

  Formula: C20H23N7O6
  Charge: -2

  ChEBI compound status: CHECKED (C)

  

  +

  L-homocysteine

  L-homocysteine

  Name origin: UniProt - CHECKED (C)

  CHEBI:58199

  Formula: C4H9NO2S
  Charge: 0

  ChEBI compound status: CHECKED (C)

  

  =

  (6S)-5,6,7,8-tetrahydrofolate

  (6S)-5,6,7,8-tetrahydrofolate

  Name origin: UniProt - CHECKED (C)

  CHEBI:57453

  Formula: C19H21N7O6
  Charge: -2

  ChEBI compound status: CHECKED (C)

  

  +

  L-methionine

  L-methionine

  Name origin: UniProt - CHECKED (C)

  CHEBI:57844

  Formula: C5H11NO2S
  Charge: 0

  ChEBI compound status: CHECKED (C)

  

Cofactors

• cob(II)alamin
• Zn²⁺

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.

Links to other databases

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: 228-234 (1969). [PMID: 5799642]
2. Foster, M.A., Dilworth, M.J. and Woods, D.D.
   Cobalamin and the synthesis of methionine by Escherichia coli.
   Nature 201: 39-42 (1964).
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: 497-504 (1964).
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: 2888-2895 (1964).
5. Taylor, R.T.
   Escherichia coli B N⁵-methyltetrahydrofolate-homocysteine cobalamin methyltransferase: gel-filtration behavior of apoenzyme and holoenzymes.
   Biochim. Biophys. Acta 242: 355-364 (1971). [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: 5372-5382 (1998). [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: 8410-8416 (1998).
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: 10711-10719 (2000). [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: 53-56 (2002). [PMID: 11731805]

[EC 2.1.1.13 created 1972, modified 2003]