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PROSITE documentation PDOC50970 [for PROSITE entry PS50970]

Homocysteine-binding domain profile


The homocysteine (Hcy) binding domain is an ~300-residue module which is found in a set of enzymes involved in alkyl transfer to thiols:

  • Prokaryotic and eukaryotic B12-dependent methionine synthase (MetH) (EC, a large, modular protein that catalyses the transfer of a methyl group from methyltetrahydrofolate (CH3-H4folate) to Hcy to form methionine, using cobalamin as an intermediate methyl carrier.
  • Mammalian βine-homocysteine S-methyltransferase (BHMT) (EC It catalyzes the transfer of a methyl group from glycine βine to Hcy, forming methionine and dimethylglycine.
  • Plant selenocysteine methyltransferase (EC 2.1.1.-).
  • Plant and fungal AdoMet homocysteine S-methyltransferases (EC

The Hcy-binding domain utilizes a Zn(Cys)3 cluster to bind and activate Hcy. It has been shown to form a (β/α)8 barrel (see <PDB:1Q7Z>). The Hcy binding domain barrel is distorted to form the metal- and substrate-binding sites. To accommodate the substrate, strands 1 and 2 of the barrel are loosely joined by nonclassic hydrogen bonds; to accommodate the metal, strands 6 and 8 are drawn together and strand 7 is extruded from the end of the barrel. The cysteines ligating the catalytic zinc atom are located at the C-terminal ends of strands 6 and 8 [1,2].

The profile we developed covers the entire Hcy domain.

Last update:

October 2005 / Text revised.

Technical section

PROSITE method (with tools and information) covered by this documentation:

HCY, PS50970; Homocysteine-binding domain profile  (MATRIX)


1AuthorsEvans J.C., Huddler D.P., Jiracek J., Castro C., Millian N.S., Garrow T.A., Ludwig M.L.
TitleBetaine-homocysteine methyltransferase: zinc in a distorted barrel.
SourceStructure 10:1159-1171(2002).
PubMed ID12220488

2AuthorsEvans J.C., Huddler D.P., Hilgers M.T., Romanchuk G., Matthews R.G., Ludwig M.L.
TitleStructures of the N-terminal modules imply large domain motions during catalysis by methionine synthase.
SourceProc. Natl. Acad. Sci. U.S.A. 101:3729-3736(2004).
PubMed ID14752199

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