Four cysteine residues and one residue, which is either serine or threonine, are identified as likely active-site residues.[1] Solved bacterial VKOR structures has enabled more insights into the catalytic mechanism. All VKORs are transmembrane proteins with at least three TM helices at the catalytic core. The quinone to be reduced is bound by a redox-active CXXC motif in the C-terminal helices, similar to the DsbB active site. Two other cysteines to the N-terminal are located in a loop outside of the transmembrane region; they relay electrons with a redox protein (or in the case of the bacterial homolog, its own fused domain).[2][3]
The human gene for VKOR is called VKORC1 (VKOR complex subunit 1). It is the target of anticoagulantwarfarin. Its partner is a redox protein with an unknown identity,[4][5] probably a thioredoxin-like protein located in the ER lumen such as TMX1.[6]
There is also a similar gene called VKORC1L1. The VKORL1 complex it forms is much less efficient at reducing the epoxide, but it has the ability to reduce the quinone form of vitamin K to a diol form (KH2). Although EC 1.17.4.4 notes both paralogs as having both activities, the precise division of labor in vitro is debated.[7]
References
^ abcGoodstadt L, Ponting CP (June 2004). "Vitamin K epoxide reductase: homology, active site and catalytic mechanism". Trends in Biochemical Sciences. 29 (6): 289–92. doi:10.1016/j.tibs.2004.04.004. PMID15276181.
