{PDOC50970} {PS50970; HCY} {BEGIN} *************************************** * 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 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 (see ). 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. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: October 2005 / Text revised. [ 1] Evans J.C., Huddler D.P., Jiracek J., Castro C., Millian N.S., Garrow T.A., Ludwig M.L. "Betaine-homocysteine methyltransferase: zinc in a distorted barrel." Structure 10:1159-1171(2002). PubMed=12220488 [ 2] Evans J.C., Huddler D.P., Hilgers M.T., Romanchuk G., Matthews R.G., Ludwig M.L. "Structures of the N-terminal modules imply large domain motions during catalysis by methionine synthase." Proc. Natl. Acad. Sci. U.S.A. 101:3729-3736(2004). PubMed=14752199; DOI=10.1073/pnas.0308082100 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}