This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
6wv4
From Proteopedia
Human VKOR C43S with warfarin
Structural highlights
DiseaseVKOR1_HUMAN Prediction of resistance to vitamin K antagonists;Prediction of toxicity or dose selection of vitamin K antagonists;Hereditary combined deficiency of vitamin K-dependent clotting factors. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. FunctionK0NYR4_9CAUD 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.VKOR1_HUMAN Involved in vitamin K metabolism. Catalytic subunit of the vitamin K epoxide reductase (VKOR) complex which reduces inactive vitamin K 2,3-epoxide to active vitamin K. Vitamin K is required for the gamma-carboxylation of various proteins, including clotting factors, and is required for normal blood coagulation, but also for normal bone development.[1] [2] [3] [4] [5] [6] [7] 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[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
