PROSITE documentation PDOC50970Homocysteine-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 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.
Last update:October 2005 / Text revised.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Evans J.C. Huddler D.P. Jiracek J. Castro C. Millian N.S. Garrow T.A. Ludwig M.L. |
| Title | Betaine-homocysteine methyltransferase: zinc in a distorted barrel. | |
| Source | Structure 10:1159-1171(2002). | |
| PubMed ID | 12220488 |
| 2 | Authors | Evans J.C. Huddler D.P. Hilgers M.T. Romanchuk G. Matthews R.G. Ludwig M.L. |
| Title | Structures of the N-terminal modules imply large domain motions during catalysis by methionine synthase. | |
| Source | Proc. Natl. Acad. Sci. U.S.A. 101:3729-3736(2004). | |
| PubMed ID | 14752199 | |
| DOI | 10.1073/pnas.0308082100 |
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