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Structure of a bacterial homologue of vitamin K epoxide reductase.

<div class='caption-title'>Architecture of Synechococcus VKOR in complex with its redox partner</div>
<div class='caption-title'>The active site of VKOR</div>
<div class='caption-title'>Mutations causing warfarin resistance in mammalian VKOR</div>
Li W, Schulman S, Dutton RJ, Boyd D, Beckwith J, Rapoport TA
OpenAccess logo Nature 463 507-12 (2010)
Cited: 116 times
EuropePMC logo PMID: 20110994

Abstract

Vitamin 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.

Reviews - 3kp8 mentioned but not cited (1)

  1. Macromolecular ab initio phasing enforcing secondary and tertiary structure. Millán C, Sammito M, Usón I. IUCrJ 2 95-105 (2015)

Articles - 3kp8 mentioned but not cited (2)

  1. Structure of a bacterial homologue of vitamin K epoxide reductase. Li W, Schulman S, Dutton RJ, Boyd D, Beckwith J, Rapoport TA. Nature 463 507-512 (2010)
  2. The geometry of Niggli reduction: SAUC - search of alternative unit cells. McGill KJ, Asadi M, Karakasheva MT, Andrews LC, Bernstein HJ. J Appl Crystallogr 47 360-364 (2014)


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