Betaine-homocysteine methyltransferase: Zinc in a distorted barrel

被引：105

作者：

Evans, JC

Huddler, DP

Jiracek, J

Castro, C

Millian, NS

Garrow, TA

Ludwig, ML ^{[1
]}

机构：

[1] Univ Michigan, Div Biophys Res, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA

[3] Acad Sci Czech Republ, Inst Organ Chem & Biochem, Dept Peptide Biochem, CR-16610 Prague, Czech Republic

[4] Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA

来源：

STRUCTURE | 2002年 / 10卷 / 09期

关键词：

homocysteine; zinc; methyltransfer(beta/alpha)(8) barrel; thiolate ligands; signature sequences;

D O I：

10.1016/S0969-2126(02)00796-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Betaine-homocysteine methyl transferase (BHMT) catalyzes the synthesis of methionine from betaine and homocysteine (Hcy), utilizing a zinc ion to activate Hcy. BHMT is a key liver enzyme that is important for homocysteine homeostasis. X-ray structures of human BHMT in its oxidized (Zn-free) and reduced (Zn-replete) forms, the latter in complex with the bisubstrate analog, S(delta-carboxybutyl)-L-homocysteine, were determined at resolutions of 2.15 Angstrom and 2.05 Angstrom. BHMT is a (beta/alpha)(8) barrel that is distorted to construct the substrate and metal binding sites. The zinc binding sequences G-V/L-N-C and G-G-C-C are at the C termini of strands beta6 and beta8. Oxidation to the Cys217-Cys299 disulfide and expulsion of Zn are accompanied by local rearrangements. The structures identify Hcy binding fingerprints and provide a prototype for the homocysteine S-methyltransferase family.

引用

页码：1159 / 1171

页数：13

共 64 条

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