6WV4

Human VKOR C43S with warfarin

6WV4 の概要

• エントリーDOI: 10.2210/pdb6wv4/pdb
• 分子名称: Vitamin K epoxide reductase Cys43Ser mutant, termini restrained by green fluorescent protein, S-WARFARIN (3 entities in total)
• 機能のキーワード: vitamin k epoxide reductase (vkor), vitamin k, warfarin, superwarfarin, vitamin k expoxide(ko), membrane protein, oxidoreductase, fluorescent protein
• 由来する生物種: Aequorea victoria (Jellyfish); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 44489.70

構造登録者

Liu, S.,Sukumar, N.,Li, W. (登録日: 2020-05-05, 公開日: 2020-11-11, 最終更新日: 2024-11-13)

主引用文献

Liu, S.,Li, S.,Shen, G.,Sukumar, N.,Krezel, A.M.,Li, W.
Structural basis of antagonizing the vitamin K catalytic cycle for anticoagulation.
Science, 371:-, 2021

PubMed Abstract: Vitamin K antagonists are widely used anticoagulants that target vitamin K epoxide reductases (VKOR), a family of integral membrane enzymes. To elucidate their catalytic cycle and inhibitory mechanism, we report 11 x-ray crystal structures of human VKOR and pufferfish VKOR-like, with substrates and antagonists in different redox states. Substrates entering the active site in a partially oxidized state form cysteine adducts that induce an open-to-closed conformational change, triggering reduction. Binding and catalysis are facilitated by hydrogen-bonding interactions in a hydrophobic pocket. The antagonists bind specifically to the same hydrogen-bonding residues and induce a similar closed conformation. Thus, vitamin K antagonists act through mimicking the key interactions and conformational changes required for the VKOR catalytic cycle.

PubMed: 33154105
DOI: 10.1126/science.abc5667

実験手法

X-RAY DIFFRACTION (3.012 Å)