VKOR

Vitamin K epoxide reductase (VKOR) is an integral membrane protein that catalyzes the reduction of vitamin K 2,3‐epoxide and vitamin K to vitamin K hydroquinone, a cofactor required for the γ‐glutamyl carboxylation reaction. The membrane topology model shows that VKOR spans the endoplasmic reticulum membrane three times with its amino‐terminus residing in the lumen and the carboxyl‐terminus residing in the cytoplasm. Both the active site (cysteines 132 and 135) and the proposed Warfarin binding site (tyrosine 139) reside in the third transmembrane helix. VKOR is the target of the widely used anticoagulant Warfarin which is proposed to exert its action by binding to the oxidized form of VKOR preventing the reduction of the essential cysteines to its active form. VKOR uses two cysteines, the CXXC redox motif, as the active site for KO reduction^[1][2].