Ontology highlight
ABSTRACT:
INSTRUMENT(S): LTQ Orbitrap
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Cell Culture, Early Embryonic Cell
SUBMITTER: Weidong Cui
LAB HEAD: Michael L. Gross
PROVIDER: PXD003774 | Pride | 2017-03-30
REPOSITORIES: Pride
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]