Member database | PROSITE profiles |
PROSITE profiles type | domain |
Short name | HCY |
Description
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 betaine-homocysteine S-methyltransferase (BHMT) (EC 2.1.1.5). It
catalyzes the transfer of a methyl group from glycine betaine 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 (beta/alpha)8 barrel. 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.
References
1.Betaine-homocysteine methyltransferase: zinc in a distorted barrel. Evans JC, Huddler DP, Jiracek J, Castro C, Millian NS, Garrow TA, Ludwig ML. Structure 10, 1159-71, (2002). View articlePMID: 12220488
2.Structures of the N-terminal modules imply large domain motions during catalysis by methionine synthase. Evans JC, Huddler DP, Hilgers MT, Romanchuk G, Matthews RG, Ludwig ML. Proc. Natl. Acad. Sci. U.S.A. 101, 3729-36, (2004). View articlePMID: 14752199