Ontology highlight
ABSTRACT:
SUBMITTER: Shen G
PROVIDER: S-EPMC5533293 | biostudies-literature | 2017 Jan
REPOSITORIES: biostudies-literature
Shen Guomin G Cui Weidong W Zhang Hao H Zhou Fengbo F Huang Wei W Liu Qian Q Yang Yihu Y Li Shuang S Bowman Gregory R GR Sadler J Evan JE Gross Michael L ML Li Weikai W
Nature structural & molecular biology 20161205 1
Although warfarin is the most widely used anticoagulant worldwide, the mechanism by which warfarin inhibits its target, human vitamin K epoxide reductase (hVKOR), remains unclear. Here we show that warfarin blocks a dynamic electron-transfer process in hVKOR. A major fraction of cellular hVKOR is in an intermediate redox state containing a Cys51-Cys132 disulfide, a characteristic accommodated by a four-transmembrane-helix structure of hVKOR. Warfarin selectively inhibits this major cellular form ...[more]