3KP9

Structure of a bacterial homolog of vitamin K epoxide reductase

3KP9 の概要

• エントリーDOI: 10.2210/pdb3kp9/pdb
• 関連するPDBエントリー: 3KP8
• 分子名称: VKORC1/thioredoxin domain protein, UBIQUINONE-10, MERCURY (II) ION (3 entities in total)
• 機能のキーワード: warfarin, disulfide formation, blood coagulation, oxidoreductase
• 由来する生物種: Synechococcus sp.
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 32933.30

構造登録者

Li, W.,Schulman, S.,Dutton, R.J.,Boyd, D.,Beckwith, J.,Rapoport, T.A. (登録日: 2009-11-16, 公開日: 2010-02-09, 最終更新日: 2024-11-20)

主引用文献

Li, W.,Schulman, S.,Dutton, R.J.,Boyd, D.,Beckwith, J.,Rapoport, T.A.
Structure of a bacterial homologue of vitamin K epoxide reductase.
Nature, 463:507-512, 2010

PubMed 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.

PubMed: 20110994
DOI: 10.1038/nature08720

実験手法

X-RAY DIFFRACTION (3.6 Å)