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 2.1.1.13), 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 2.1.1.5). 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 2.1.1.10).

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.