ArticleThe Journal of biological chemistry2013
Chloroquine binding reveals flavin redox switch function of quinone reductase 2.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 41 citations in OpenAlex.
- Insights into the cellular function and mechanism of action of quinone reductase 2 (NQO2).The Biochemical journal · 2025Review
- Evolutionary analysis of Quinone Reductases 1 and 2 suggests that NQO2 evolved to function as a pseudoenzyme.Protein science : a publication of the Protein Society · 2024Article
- Probing the metalloproteome: an 8-mercaptoquinoline motif enriches minichromosome maintenance complex components as significant metalloprotein targets in live cells.RSC chemical biology · 2024Article
- The Unusual Cosubstrate Specificity of NQO2: Conservation Throughout the Amniotes and Implications for Cellular Function.Frontiers in pharmacology · 2022Article
- Apigenin and Luteolin Regulate Autophagy by Targeting NRH-Quinone Oxidoreductase 2 in Liver Cells.Antioxidants (Basel, Switzerland) · 2021Article
- The diverse functionality of NQO1 and its roles in redox control.Redox biology · 2021Review
- Is Antioxidant Therapy a Useful Complementary Measure for Covid-19 Treatment? An Algorithm for Its Application.Medicina (Kaunas, Lithuania) · 2020Review
- Curcumin Derivatives Verify the Essentiality of ROS Upregulation in Tumor Suppression.Molecules (Basel, Switzerland) · 2019Article
- Pentagamavunon-1 (PGV-1) inhibits ROS metabolic enzymes and suppresses tumor cell growth by inducing M phase (prometaphase) arrest and cell senescence.Scientific reports · 2019Article
- Cyclic Changes in Active Site Polarization and Dynamics Drive the 'Ping-pong' Kinetics in NRH:Quinone Oxidoreductase 2: An Insight from QM/MM Simulations.ACS catalysis · 2018Article
- Reduction and Scavenging of Chemically Reactive Drug Metabolites by NAD(P)H:Quinone Oxidoreductase 1 and NRH:Quinone Oxidoreductase 2 and Variability in Hepatic Concentrations.Chemical research in toxicology · 2018Article
- Structure, function, and mechanism of proline utilization A (PutA).Archives of biochemistry and biophysics · 2017Review
- Role of Quinone Reductase 2 in the Antimalarial Properties of Indolone-Type Derivatives.Molecules (Basel, Switzerland) · 2017Article
- Insight into the kinetics and thermodynamics of the hydride transfer reactions between quinones and lumiflavin: a density functional theory study.Journal of molecular modeling · 2016Article
- Active-Site Plasticity Is Essential to Carbapenem Hydrolysis by OXA-58 Class D β-Lactamase of Acinetobacter baumannii.Antimicrobial agents and chemotherapy · 2016Article
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Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Quinone reductase 2 (NQO2) is an FAD-linked enzyme and the only known human target of two antimalarial drugs, primaquine (PQ) and chloroquine (CQ). The structural differences between oxidized and reduced NQO2 and the structural basis for inhibition by PQ and CQ were investigated by x-ray crystallography. Structures of oxidized NQO2 in complex with PQ and CQ were solved at 1.4 Å resolution. CQ binds preferentially to reduced NQO2, and upon reduction of NQO2-CQ crystals, the space group changed from P2(1)2(1)2(1) to P2(1), with 1-Å decreases in all three unit cell dimensions. The change in crystal packing originated in the negative charge and 4-5º bend in the reduced isoalloxazine ring of FAD, which resulted in a new mode of CQ binding and closure of a flexible loop (Phe(126)-Leu(136)) over the active site. This first structure of a reduced quinone reductase shows that reduction of the FAD cofactor and binding of a specific inhibitor lead to global changes in NQO2 structure and is consistent with a functional role for NQO2 as a flavin redox switch.
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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.