ArticleNature communications2014
Structures of an intramembrane vitamin K epoxide reductase homolog reveal control mechanisms for electron transfer.
Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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Who cites it
24 citing papers in PubMed, 45 citations in OpenAlex.
- Isomer-Dependent Pharmacokinetic Behavior and VKOR Interactions of Second-Generation Anticoagulant Rodenticides: An Integrated In Vivo-In Vitro-In Silico Investigation.International journal of molecular sciences · 2026Article
- Synergy of Mutation-Induced Effects in Human Vitamin K Epoxide Reductase: Perspectives and Challenges for Allo-Network Modulator Design.International journal of molecular sciences · 2024Article
- Distinct enzymatic strategies forCritical reviews in biochemistry and molecular biology · 2023Article
- Structural features determining the vitamin K epoxide reduction activity in the VKOR family of membrane oxidoreductases.The FEBS journal · 2022Article
- Structural basis of antagonizing the vitamin K catalytic cycle for anticoagulation.Science (New York, N.Y.) · 2021Article
- Termini restraining of small membrane proteins enables structure determination at near-atomic resolution.Science advances · 2020Article
- Article
- Characterization of Warfarin Inhibition Kinetics Requires Stabilization of Intramembrane Vitamin K Epoxide Reductases.Journal of molecular biology · 2020Article
- Structural Insights into Phylloquinone (Vitamin K1), Menaquinone (MK4, MK7), and Menadione (Vitamin K3) Binding to VKORC1.Nutrients · 2019Article
- Membrane properties that shape the evolution of membrane enzymes.Current opinion in structural biology · 2018Review
- VKORC1L1, An Enzyme Mediating the Effect of Vitamin K in Liver and Extrahepatic Tissues.Nutrients · 2018Review
- Stabilization of warfarin-binding pocket of VKORC1 and VKORL1 by a peripheral region determines their different sensitivity to warfarin inhibition.Journal of thrombosis and haemostasis : JTH · 2018Article
- Chemistry and Enzymology of Disulfide Cross-Linking in Proteins.Chemical reviews · 2018Review
- Membrane Protein Structure in Live Cells: Methodology for Studying Drug Interaction by Mass Spectrometry-Based Footprinting.Biochemistry · 2018Article
- Intramembrane Thiol Oxidoreductases: Evolutionary Convergence and Structural Controversy.Biochemistry · 2018Article
- Structural basis for catalysis at the membrane-water interface.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2017Review
- New pieces to an old puzzle: identifying the warfarin-binding site that prevents clotting.Nature structural & molecular biology · 2017Article
- Warfarin and vitamin K compete for binding to Phe55 in human VKOR.Nature structural & molecular biology · 2017Article
- Warfarin traps human vitamin K epoxide reductase in an intermediate state during electron transfer.Nature structural & molecular biology · 2017Article
- Tautomerism of Warfarin: Combined Chemoinformatics, Quantum Chemical, and NMR Investigation.The Journal of organic chemistry · 2015Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The intramembrane vitamin K epoxide reductase (VKOR) supports blood coagulation in humans and is the target of the anticoagulant warfarin. VKOR and its homologues generate disulphide bonds in organisms ranging from bacteria to humans. Here, to better understand the mechanism of VKOR catalysis, we report two crystal structures of a bacterial VKOR captured in different reaction states. These structures reveal a short helix at the hydrophobic active site of VKOR that alters between wound and unwound conformations. Motions of this 'horizontal helix' promote electron transfer by regulating the positions of two cysteines in an adjacent loop. Winding of the helix separates these 'loop cysteines' to prevent backward electron flow. Despite these motions, hydrophobicity at the active site is maintained to facilitate VKOR catalysis. Biochemical experiments suggest that several warfarin-resistant mutations act by changing the conformation of the horizontal helix. Taken together, these studies provide a comprehensive understanding of VKOR function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.