ArticleAntioxidants (Basel, Switzerland)2020
The Catalytic Cycle of the Antioxidant and Cancer-Associated Human NQO1 Enzyme: Hydride Transfer, Conformational Dynamics and Functional Cooperativity.
Article in Antioxidants (Basel, Switzerland), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Tyrosine residues at the substrate binding site in human NQO1 homodimer: Protein conformational dynamics and optimization of substrate binding geometry.The FEBS journal · 2026Article
- Free Radical Formation in the Reactions of Redox-Active Drugs and Xenobiotics with Mitochondrial Flavoenzymes.Biomolecules · 2026Review
- Recent advances in drug repositioning and rediscovery for different therapeutic activities utilizing updated technological approaches.Molecular diversity · 2026Review
- Minimized sample consumption for time-resolved serial crystallography applied to the redox cycle of human NQO1.Communications chemistry · 2026Article
- Mechanism of cyanobacterial ferredoxin-dependent flavin thioredoxin reductase reveals thiolate-FAD charge transfer and catalytic asymmetry in a homodimer.The FEBS journal · 2026Article
- Innovative Strategies in X-ray Crystallography for Exploring Structural Dynamics and Reaction Mechanisms in Metabolic Disorders.Journal of personalized medicine · 2024Review
- Structural dynamics and functional cooperativity of human NQO1 by ambient temperature serial crystallography and simulations.Protein science : a publication of the Protein Society · 2024Article
- Modular droplet injector for sample conservation providing new structural insight for the conformational heterogeneity in the disease-associated NQO1 enzyme.Lab on a chip · 2023Article
- Phenotypic Modulation of Cancer-Associated Antioxidant NQO1 Activity by Post-Translational Modifications and the Natural Diversity of the Human Genome.Antioxidants (Basel, Switzerland) · 2023Review
- Riboflavin kinase and pyridoxine 5'-phosphate oxidase complex formation envisages transient interactions for FMN cofactor delivery.Frontiers in molecular biosciences · 2023Article
- Roles of Ferredoxin-NADPAntioxidants (Basel, Switzerland) · 2022Review
- Allosteric Communication in the Multifunctional and Redox NQO1 Protein Studied by Cavity-Making Mutations.Antioxidants (Basel, Switzerland) · 2022Article
- Targeting HIF-1α Function in Cancer through the Chaperone Action of NQO1: Implications of Genetic Diversity of NQO1.Journal of personalized medicine · 2022Review
- Mining the Flavoproteome of Brucella ovis, the Brucellosis Causing Agent in Ovis aries.Microbiology spectrum · 2022Article
- Effect of naturally-occurring mutations on the stability and function of cancer-associated NQO1: Comparison of experiments and computation.Frontiers in molecular biosciences · 2022Article
- Article
- Single- and Two-Electron Reduction of Nitroaromatic Compounds by Flavoenzymes: Mechanisms and Implications for Cytotoxicity.International journal of molecular sciences · 2021Review
- The diverse functionality of NQO1 and its roles in redox control.Redox biology · 2021Review
- Naturally-Occurring Rare Mutations Cause Mild to Catastrophic Effects in the Multifunctional and Cancer-Associated NQO1 Protein.Journal of personalized medicine · 2020Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Human NQO1 [NAD(H):quinone oxidoreductase 1] is a multi-functional and stress-inducible dimeric protein involved in the antioxidant defense, the activation of cancer prodrugs and the stabilization of oncosuppressors. Despite its roles in human diseases, such as cancer and neurological disorders, a detailed characterization of its enzymatic cycle is still lacking. In this work, we provide a comprehensive analysis of the NQO1 catalytic cycle using rapid mixing techniques, including multiwavelength and spectral deconvolution studies, kinetic modeling and temperature-dependent kinetic isotope effects (KIEs). Our results systematically support the existence of two pathways for hydride transfer throughout the NQO1 catalytic cycle, likely reflecting that the two active sites in the dimer catalyze two-electron reduction with different rates, consistent with the cooperative binding of inhibitors such as dicoumarol. This negative cooperativity in NQO1 redox activity represents a sort of half-of-sites activity. Analysis of KIEs and their temperature dependence also show significantly different contributions from quantum tunneling, structural dynamics and reorganizations to catalysis at the two active sites. Our work will improve our understanding of the effects of cancer-associated single amino acid variants and post-translational modifications in this protein of high relevance in cancer progression and treatment.
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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.