ArticleNature structural & molecular biology2017
Warfarin and vitamin K compete for binding to Phe55 in human VKOR.
Article in Nature structural & molecular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 49 citations in OpenAlex.
- Protein S: a vitamin K-dependent factor bridging haemostasis, tissue homeostasis and cancer.The Biochemical journal · 2026Review
- Sex-Related Effect of Chronic Doses of Warfarin and Menadione onInternational journal of molecular sciences · 2026Article
- Structural disruption of VKORC1 by resistance mutations reveals a conserved hydrophobic pattern essential for warfarin binding: insights from molecular dynamics analyses.Molecular diversity · 2026Article
- 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
- Detection of Vkorc1 single nucleotide polymorphisms indicates the presence of anticoagulant rodenticide resistance in Australia's introduced ratsPest management science · 2025Article
- Effect of Warfarin on Lifespan and Oxidative Stress Tolerance ofInternational journal of molecular sciences · 2025Article
- Drug-microbiota interactions: an emerging priority for precision medicine.Signal transduction and targeted therapy · 2023Review
- Vitamin K-Dependent Protein Activation: Normal Gamma-Glutamyl Carboxylation and Disruption in Disease.International journal of molecular sciences · 2022Review
- A novel graph mining approach to predict and evaluate food-drug interactions.Scientific reports · 2022Article
- Vitamin K-Dependent Proteins in Skeletal Development and Disease.International journal of molecular sciences · 2021Review
- A novel vitamin K derived anticoagulant tolerant to genetic variations of vitamin K epoxide reductase.Journal of thrombosis and haemostasis : JTH · 2021Article
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- Comparison of two reducing agents dithiothreitol and tris(3-hydroxypropyl)phosphine forVeterinary and animal science · 2020Article
- Superwarfarin (Long-Acting Anticoagulant Rodenticides) Poisoning: from Pathophysiology to Laboratory-Guided Clinical Management.The Clinical biochemist. Reviews · 2019Review
- Determining the necessity of phenyl ring π-character in warfarin.Bioorganic & medicinal chemistry letters · 2019Article
- Multiple Modes of Vitamin K Actions in Aging-Related Musculoskeletal Disorders.International journal of molecular sciences · 2019Review
- Structural Insights into Phylloquinone (Vitamin K1), Menaquinone (MK4, MK7), and Menadione (Vitamin K3) Binding to VKORC1.Nutrients · 2019Article
- Stability of warfarin sodium flavoured preservative-free oral liquid formulations.European journal of hospital pharmacy : science and practice · 2018Article
- Missense mutation of VKORC1 leads to medial arterial calcification in rats.Scientific reports · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vitamin K epoxide reductase (VKOR) catalyzes the reduction of vitamin K quinone and vitamin K 2,3-epoxide, a process essential to sustain γ-carboxylation of vitamin K-dependent proteins. VKOR is also a therapeutic target of warfarin, a treatment for thrombotic disorders. However, the structural and functional basis of vitamin K reduction and the antagonism of warfarin inhibition remain elusive. Here, we identified putative binding sites of both K vitamers and warfarin on human VKOR. The predicted warfarin-binding site was verified by shifted dose-response curves of specified mutated residues. We used CRISPR-Cas9-engineered HEK 293T cells to assess the vitamin K quinone and vitamin K 2,3-epoxide reductase activities of VKOR variants to characterize the vitamin K naphthoquinone head- and isoprenoid side chain-binding regions. Our results challenge the prevailing concept of noncompetitive warfarin inhibition because K vitamers and warfarin share binding sites on VKOR that include Phe55, a key residue binding either the substrate or inhibitor.
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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.