6WV8
Takifugu rubripes VKOR-like C138S mutant with vitamin K1
Summary for 6WV8
| Entry DOI | 10.2210/pdb6wv8/pdb |
| Descriptor | Vitamin K epoxide reductase-like protein, termini restrained by green fluorescent protein, PHYLLOQUINONE (3 entities in total) |
| Functional Keywords | vitamin k epoxide reductase, vkor, vkor-like protein, vkorl, membrane protein |
| Biological source | Escherichia virus RB43 More |
| Total number of polymer chains | 1 |
| Total formula weight | 47217.21 |
| Authors | Liu, S.,Sukumar, N.,Li, W. (deposition date: 2020-05-05, release date: 2020-11-11, Last modification date: 2024-10-16) |
| 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 (3.01 Å) |
Structure validation
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