哺乳动物维他命K环氧化物还原酶（VKOR）催化对维他命K苯二酚的生成，这是维他命K循环中的决定性一步，是血液凝固所必需的。
现在，VKOR 的一个细菌同源分子的X-射线晶体结构已被确定。该结构所反映的VKOR 存在于跟其氧化还原伙伴（一个与硫氧还蛋白相似的区域）形成的一个复合物中，它相应于电子转移的抑制状态。这个发现为VKOR 利用来自新合成的蛋白还原苯醌指出了一个可能的机制。这项工作可帮助解释VKOR 发生的突变何以能够引起对“华法令”（或称“华法林”）的抵抗力，后者是通过抑制VKOR发挥作用的普遍使用的抗凝血剂。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
