4NV5

C50A mutant of Synechococcus VKOR, C2 crystal form (dehydrated)

4NV5 の概要

• エントリーDOI: 10.2210/pdb4nv5/pdb
• 関連するPDBエントリー: 3KP8 3KP9 4NV2 4NV6
• 分子名称: VKORC1/thioredoxin domain protein, UBIQUINONE-10 (2 entities in total)
• 機能のキーワード: four helix bundle, oxidoreductase, thioredoxin-like protein, membrane
• 由来する生物種: Synechococcus sp.
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 65032.24

構造登録者

Liu, S.,Cheng, W.,Fowle Grider, R.,Shen, G.,Li, W. (登録日: 2013-12-04, 公開日: 2014-02-12, 最終更新日: 2024-10-09)

主引用文献

Liu, S.,Cheng, W.,Fowle Grider, R.,Shen, G.,Li, W.
Structures of an intramembrane vitamin K epoxide reductase homolog reveal control mechanisms for electron transfer.
Nat Commun, 5:3110-3110, 2014

PubMed Abstract: The intramembrane vitamin K epoxide reductase (VKOR) supports blood coagulation in humans and is the target of the anticoagulant warfarin. VKOR and its homologues generate disulphide bonds in organisms ranging from bacteria to humans. Here, to better understand the mechanism of VKOR catalysis, we report two crystal structures of a bacterial VKOR captured in different reaction states. These structures reveal a short helix at the hydrophobic active site of VKOR that alters between wound and unwound conformations. Motions of this 'horizontal helix' promote electron transfer by regulating the positions of two cysteines in an adjacent loop. Winding of the helix separates these 'loop cysteines' to prevent backward electron flow. Despite these motions, hydrophobicity at the active site is maintained to facilitate VKOR catalysis. Biochemical experiments suggest that several warfarin-resistant mutations act by changing the conformation of the horizontal helix. Taken together, these studies provide a comprehensive understanding of VKOR function.

PubMed: 24477003
DOI: 10.1038/ncomms4110

実験手法

X-RAY DIFFRACTION (2.79 Å)