6wva | pdb_00006wva
Takifugu rubripes VKOR-like with vitamin K1 epoxide at non-catalytic state
Structural highlights
FunctionVKORL_TAKRU Involved in vitamin K metabolism (PubMed:33154105). Can reduce inactive vitamin K 2,3-epoxide to active vitamin K, and may contribute to vitamin K-mediated protection against oxidative stress (PubMed:33154105). Plays a role in vitamin K-dependent gamma-carboxylation of Glu residues in target proteins (By similarity).[UniProtKB:Q8N0U8][1] GFP_AEQVI Energy-transfer acceptor. Its role is to transduce the blue chemiluminescence of the protein aequorin into green fluorescent light by energy transfer. Fluoresces in vivo upon receiving energy from the Ca(2+)-activated photoprotein aequorin. Publication Abstract from PubMedVitamin 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
