ArticleNature communications2015
Structural basis of DNA gyrase inhibition by antibacterial QPT-1, anticancer drug etoposide and moxifloxacin.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
72 citing papers in PubMed, 155 citations in OpenAlex.
- Genetic mutations driving ciprofloxacin resistance in laboratory-evolvedMicrobiology spectrum · 2026Article
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- Synthesis and Antimicrobial Activity of Novel Fluoroquinolone with Geranyl Amine Moiety.Current issues in molecular biology · 2026Article
- Structural and Computational Analysis ofBiomolecules · 2026Article
- Gyrase and Topoisomerase IV as Antibacterial Targets for Gepotidacin and Zoliflodacin: Teaching Old Enzymes New Tricks.International journal of molecular sciences · 2026Review
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- Spirobarbiturates with a pyrrolizidine moiety: synthesis, structure and biological evaluation.Beilstein journal of organic chemistry · 2026Article
- All-atoms MD simulations study of newly designed ciprofloxacin derivatives as potential bacterial DHPS and DNA gyrase inhibitors.Frontiers in bioinformatics · 2026Article
- Structural and Computational Analysis ofbioRxiv : the preprint server for biology · 2025Article
- Mechanism of Action of Gepotidacin: Well-Balanced Dual-Targeting againstACS infectious diseases · 2025Article
- Drug Repurposing: An Emerging Strategy inJournal of microbiology and biotechnology · 2025Review
- Structural Mechanisms of Topoisomerase-Targeting Drugs.Annual review of biochemistry · 2025Review
- Recent advancements in the development of next-generation dual-targeting antibacterial agents.RSC medicinal chemistry · 2025Review
- Natural Variation ofInternational journal of molecular sciences · 2025Article
- Review
- Synthesis and Evaluation of Antibacterial and Antifungal ActivitiesMedicinal chemistry (Shariqah (United Arab Emirates)) · 2025Article
- DNA Cleavage Mediated by Bacterial Type II Topoisomerases.Methods in molecular biology (Clifton, N.J.) · 2025Article
- DNA Decatenation Catalyzed by Bacterial Topoisomerase IV.Methods in molecular biology (Clifton, N.J.) · 2025Article
- DNA Supercoiling Catalyzed by Bacterial Gyrase.Methods in molecular biology (Clifton, N.J.) · 2025Article
- How Do Gepotidacin and Zoliflodacin Stabilize DNA-Cleavage Complexes with Bacterial Type IIA Topoisomerases? 2. A Single Moving Metal Mechanism.International journal of molecular sciences · 2024Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
Abstract
New antibacterials are needed to tackle antibiotic-resistant bacteria. Type IIA topoisomerases (topo2As), the targets of fluoroquinolones, regulate DNA topology by creating transient double-strand DNA breaks. Here we report the first co-crystal structures of the antibacterial QPT-1 and the anticancer drug etoposide with Staphylococcus aureus DNA gyrase, showing binding at the same sites in the cleaved DNA as the fluoroquinolone moxifloxacin. Unlike moxifloxacin, QPT-1 and etoposide interact with conserved GyrB TOPRIM residues rationalizing why QPT-1 can overcome fluoroquinolone resistance. Our data show etoposide's antibacterial activity is due to DNA gyrase inhibition and suggests other anticancer agents act similarly. Analysis of multiple DNA gyrase co-crystal structures, including asymmetric cleavage complexes, led to a 'pair of swing-doors' hypothesis in which the movement of one DNA segment regulates cleavage and religation of the second DNA duplex. This mechanism can explain QPT-1's bacterial specificity. Structure-based strategies for developing topo2A antibacterials are suggested.
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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.