This entry represents the vitamin K epoxide reductase complex subunit VKORC1 and VKORC1L1 mostly from animals.VKORC1 is an integral membrane protein that catalyzes the reduction of vitamin K 2,3-epoxide and vitamin K to vitamin K hydroquinone, an essential co-factor subsequently used in the γ-carboxylation of glutamic acid residues in blood coagulation enzymes [, ]. All homologues of VKOR contain an active site CXXC motif, which is switched between reduced and disulfide-bonded states during the reaction cycle []. Warfarin, a widely used oral anticoagulant used in medicine as well as rodenticides, inhibits the activity of VKOR, resulting in decreased levels of reduced vitamin K, which is required for the function of several clotting factors []. However, anticoagulation effect of warfarin is significantly associated with polymorphism of certain genes, including VKORC1. Interestingly, in rodents, an adaptive trait appears to have evolved convergently by selection on new or standing genetic polymorphisms in VKORC1 as well as by adaptive introgressive hybridization between species, likely brought about by human-mediated dispersal []. VKORC1L1, a paralogue of VKORC1, is a vitamin K oxidoreductase, which can support γ-carboxylation in vivo [, ].
Vitamin K epoxide reductase (VKOR) recycles vitamin K 2,3-epoxide to vitamin K hydroquinone, a co-factor that is essential for the posttranslational γ-carboxylation of several blood coagulation factors []. VKORC1, the catalytic subunit of the VKOR complex, is a member of a large family of predicted enzymes that are present in vertebrates, Drosophila, plants, bacteria and archaea [, ]. Bacterial VKOR homologues catalyse disulphide bridge formation in secreted proteins by cooperating with a periplasmic, Trx-like redox partner [, ]. In fact, in some plant and bacterial homologues the VKORC1 homologous domain is fused with domains of the thioredoxin family of oxidoreductases []. VKOR is part of a disulphide bond formation pathway that uses electrons from cysteines of newly synthesized proteins to reduce a quinone [].
Vitamin K epoxide reductase (VKOR) recycles vitamin K 2,3-epoxide to vitamin K hydroquinone, a co-factor that is essential for the posttranslational γ-carboxylation of several blood coagulation factors []. VKORC1, the catalytic subunit of the VKOR complex, is a member of a large family of predicted enzymes that are present in vertebrates, Drosophila, plants, bacteria and archaea [, ]. Bacterial VKOR homologues catalyse disulphide bridge formation in secreted proteins by cooperating with a periplasmic, Trx-like redox partner [, ]. In fact, in some plant and bacterial homologues the VKORC1 homologous domain is fused with domains of the thioredoxin family of oxidoreductases []. VKOR is part of a disulphide bond formation pathway that uses electrons from cysteines of newly synthesized proteins to reduce a quinone [].
