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6WV4

Human VKOR C43S with warfarin

Summary for 6WV4
Entry DOI10.2210/pdb6wv4/pdb
DescriptorVitamin K epoxide reductase Cys43Ser mutant, termini restrained by green fluorescent protein, S-WARFARIN (3 entities in total)
Functional Keywordsvitamin k epoxide reductase (vkor), vitamin k, warfarin, superwarfarin, vitamin k expoxide(ko), membrane protein, oxidoreductase, fluorescent protein
Biological sourceAequorea victoria (Jellyfish)
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Total number of polymer chains1
Total formula weight44489.70
Authors
Liu, S.,Sukumar, N.,Li, W. (deposition date: 2020-05-05, release date: 2020-11-11, Last modification date: 2024-11-13)
Primary citationLiu, 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
Cited by
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
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (3.012 Å)
Structure validation

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