DETERMINATION OF THE STRUCTURE OF VITAMIN K EPOXIDE REDUCTASE (VKOR)

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. VKOR reduces vitamin K epoxide to the hydroquinone form of vitamin K. Reduced vitamin K is a cofactor for a carboxylase that gamme-carboxylates several proteins, including several blood coagulation factors. VKOR is the target for warfarin, the major blood coagulation inhibitor. Homologs of VKOR exist in several bacteria and have recently been shown to be involved in disulfide bridge formation. The goal of this project is to determine an Xray structure of one of these homologs. The structure would likely shed light on the mechanism of disulfide bridge formation and warfarin inhibition.