哺乳動(dòng)物維他命K環(huán)氧化物還原酶（VKOR）催化對(duì)維他命K苯二酚的生成,，這是維他命K循環(huán)中的決定性一步,，是血液凝固所必需的,。
現(xiàn)在，VKOR 的一個(gè)細(xì)菌同源分子的X-射線晶體結(jié)構(gòu)已被確定,。該結(jié)構(gòu)所反映的VKOR 存在于跟其氧化還原伙伴（一個(gè)與硫氧還蛋白相似的區(qū)域）形成的一個(gè)復(fù)合物中,，它相應(yīng)于電子轉(zhuǎn)移的抑制狀態(tài)。這個(gè)發(fā)現(xiàn)為VKOR 利用來自新合成的蛋白還原苯醌指出了一個(gè)可能的機(jī)制,。這項(xiàng)工作可幫助解釋VKOR 發(fā)生的突變何以能夠引起對(duì)“華法令”（或稱“華法林”）的抵抗力,，后者是通過抑制VKOR發(fā)揮作用的普遍使用的抗凝血?jiǎng)＃ㄉ锕菳ioon.com）
生物谷推薦原始出處：
Nature 463, 507-512 (28 January 2010) | doi:10.1038/nature08720
Structure of a bacterial homologue of vitamin K epoxide reductase
Weikai Li1,3, Sol Schulman1,3, Rachel J. Dutton2, Dana Boyd2, Jon Beckwith2 & Tom A. Rapoport1
1 Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
2 Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
3 These authors contributed equally to this work.
4 Correspondence to: Weikai Li1,3Tom A. Rapoport1 Correspondence and requests for materials should be addressed to T.A.R. or W.L.
Vitamin K epoxide reductase (VKOR) generates vitamin K hydroquinone to sustain γ-carboxylation of many blood coagulation factors. Here, we report the 3.6?? crystal structure of a bacterial homologue of VKOR from Synechococcus sp. The structure shows VKOR in complex with its naturally fused redox partner, a thioredoxin-like domain, and corresponds to an arrested state of electron transfer. The catalytic core of VKOR is a four transmembrane helix bundle that surrounds a quinone, connected through an additional transmembrane segment with the periplasmic thioredoxin-like domain. We propose a pathway for how VKOR uses electrons from cysteines of newly synthesized proteins to reduce a quinone, a mechanism confirmed by in vitro reconstitution of vitamin K-dependent disulphide bridge formation. Our results have implications for the mechanism of the mammalian VKOR and explain how mutations can cause resistance to the VKOR inhibitor warfarin, the most commonly used oral anticoagulant.
