6WV6
Human VKOR with phenindione
Summary for 6WV6
| Entry DOI | 10.2210/pdb6wv6/pdb |
| Descriptor | Vitamin K epoxide reductase, termini restrained by green fluorescent protein, (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate, Phenindione, ... (4 entities in total) |
| Functional Keywords | vitamin k epoxide reductase (vkor), vitamin k, warfarin, superwarfarin, phenindione, vitamin k expoxide(ko), membrane protein, oxidoreductase, fluorescent protein |
| Biological source | Aequorea victoria (Jellyfish) More |
| Total number of polymer chains | 1 |
| Total formula weight | 45132.75 |
| Authors | Liu, S.,Sukumar, N.,Li, W. (deposition date: 2020-05-05, release date: 2020-11-11, Last modification date: 2024-11-06) |
| Primary citation | 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 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: 33154105DOI: 10.1126/science.abc5667 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.7 Å) |
Structure validation
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