6wv3 | pdb_00006wv3

Human VKOR with warfarin

spinqualitylabelsall models 6wv3, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6wv3 is a 1 chain structure with sequence from Aeqvi. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: OLC, SWF NonStd Res: CRO Gene: gfp (AEQVI) Activity: Oxidoreductase, with EC number 1.17.4.4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Vitamin K antagonists are widely used anticoagulants targeting vitamin K epoxide reductases (VKOR), a family of integral membrane enzymes. To elucidate their catalytic cycle and inhibitory mechanism, here we report eleven 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 a cysteine adduct that induces an open-to-closed conformational change, triggering reduction. Binding and catalysis is 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. Structural basis of antagonizing the vitamin K catalytic cycle for anticoagulation.,Liu S, Li S, Shen G, Sukumar N, Krezel AM, Li W Science. 2020 Nov 5. pii: science.abc5667. doi: 10.1126/science.abc5667. PMID:33154105 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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