Evans John C, Huddler Donald P, Jiracek Jiri, Castro Carmen, Millian Norman S, Garrow Timothy A, Ludwig Martha L
Biophysics Research Division and Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
Structure. 2002 Sep;10(9):1159-71. doi: 10.1016/s0969-2126(02)00796-7.
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 A and 2.05 A. 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.
甜菜碱-同型半胱氨酸甲基转移酶（BHMT）催化由甜菜碱和同型半胱氨酸（Hcy）合成甲硫氨酸，利用锌离子激活Hcy。BHMT是肝脏中的一种关键酶，对同型半胱氨酸的体内平衡很重要。测定了人BHMT氧化态（无锌）和还原态（富含锌）的X射线结构，后者与双底物类似物S（δ-羧基丁基）-L-同型半胱氨酸形成复合物，分辨率分别为2.15 Å和2.05 Å。BHMT是一个（β/α）8桶状结构，为构建底物和金属结合位点而发生扭曲。锌结合序列G-V/L-N-C和G-G-C-C位于β6和β8链的C末端。氧化为Cys217-Cys299二硫键并排出锌伴随着局部重排。这些结构确定了Hcy结合指纹，并为同型半胱氨酸S-甲基转移酶家族提供了一个原型。
