3kp9
Structure of a bacterial homolog of vitamin K epoxide reductase
Structural highlights
FunctionVKOR_SYNJB Thiol-disulfide oxidoreductase that catalyzes vitamin K-dependent disulfide bond formation in periplasmic target proteins.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedVitamin K epoxide reductase (VKOR) generates vitamin K hydroquinone to sustain gamma-carboxylation of many blood coagulation factors. Here, we report the 3.6 A crystal structure of a bacterial homologue of VKOR from Synechococcus sp. The structure shows VKOR in complex with its naturally fused redox partner, a thioredoxin-like domain, and corresponds to an arrested state of electron transfer. The catalytic core of VKOR is a four transmembrane helix bundle that surrounds a quinone, connected through an additional transmembrane segment with the periplasmic thioredoxin-like domain. We propose a pathway for how VKOR uses electrons from cysteines of newly synthesized proteins to reduce a quinone, a mechanism confirmed by in vitro reconstitution of vitamin K-dependent disulphide bridge formation. Our results have implications for the mechanism of the mammalian VKOR and explain how mutations can cause resistance to the VKOR inhibitor warfarin, the most commonly used oral anticoagulant. Structure of a bacterial homologue of vitamin K epoxide reductase.,Li W, Schulman S, Dutton RJ, Boyd D, Beckwith J, Rapoport TA Nature. 2010 Jan 28;463(7280):507-12. PMID:20110994[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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