ArticleNucleic acids research2013
Topoisomerase IV-quinolone interactions are mediated through a water-metal ion bridge: mechanistic basis of quinolone resistance.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 170 citations in OpenAlex.
- Novel Bacterial Topoisomerase Inhibitors: A New Front in an Old War.Journal of molecular biology · 2026Review
- Structural modeling and docking analysis of canonical and novel resistance-associated missense mutations in Sudanese Escherichia coli.Scientific reports · 2026Article
- Enzyme-DNA Interactions Affect the Catalytic Inhibition of Mycobacterial Gyrases by Antibacterial Drugs.ACS infectious diseases · 2026Article
- Activities of the Novel Bacterial Topoisomerase Inhibitor OSUAB-0284 against the Biothreat PathogenACS infectious diseases · 2026Article
- Gyrase and Topoisomerase IV as Antibacterial Targets for Gepotidacin and Zoliflodacin: Teaching Old Enzymes New Tricks.International journal of molecular sciences · 2026Review
- A Comprehensive Review on Discovery, Development, the Chemistry of Quinolones, and Their Antimicrobial Resistance.Current topics in medicinal chemistry · 2026Review
- Structural interactions of BWC0977 with Klebsiella pneumoniae topoisomerase IV and biochemical basis of its broad-spectrum activity.Communications biology · 2025Article
- Mechanism of Action of Gepotidacin: Well-Balanced Dual-Targeting againstACS infectious diseases · 2025Article
- Understanding Antibiotic Detection with Fluorescence Quantum Dots: A Review.Journal of fluorescence · 2025Review
- Chemical Proteomics Reveals Human Off-Targets of Fluoroquinolone Induced Mitochondrial Toxicity.Angewandte Chemie (International ed. in English) · 2025Article
- DNA repair is essential forJournal of bacteriology · 2025Article
- DNA repair is essential forbioRxiv : the preprint server for biology · 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
- Added insult to injury? The response of meat-associated pathogens to proposed antimicrobial interventions.Applied microbiology and biotechnology · 2024Article
- Antibacterial Mechanisms and Clinical Impact of Sitafloxacin.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Location, Location, Location: Establishing Design Principles for New Antibacterials from Ferric Siderophore Transport Systems.Molecules (Basel, Switzerland) · 2024Review
- Navigating fluoroquinolone resistance in Gram-negative bacteria: a comprehensive evaluation.JAC-antimicrobial resistance · 2024Review
- Target-Mediated Fluoroquinolone Resistance inACS infectious diseases · 2024Article
- Interactions between Gepotidacin andACS infectious diseases · 2024Article
- Gyrase and Topoisomerase IV: Recycling Old Targets for New Antibacterials to Combat Fluoroquinolone Resistance.ACS infectious diseases · 2024Review
21 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Although quinolones are the most commonly prescribed antibacterials, their use is threatened by an increasing prevalence of resistance. The most common causes of quinolone resistance are mutations of a specific serine or acidic residue in the A subunit of gyrase or topoisomerase IV. These amino acids are proposed to serve as a critical enzyme-quinolone interaction site by anchoring a water-metal ion bridge that coordinates drug binding. To probe the role of the proposed water-metal ion bridge, we characterized wild-type, GrlA(E85K), GrlA(S81F/E85K), GrlA(E85A), GrlA(S81F/E85A) and GrlA(S81F) Bacillus anthracis topoisomerase IV, their sensitivity to quinolones and related drugs and their use of metal ions. Mutations increased the Mg(2+) concentration required to produce maximal quinolone-induced DNA cleavage and restricted the divalent metal ions that could support quinolone activity. Individual mutation of Ser81 or Glu85 partially disrupted bridge function, whereas simultaneous mutation of both residues abrogated protein-quinolone interactions. Results provide functional evidence for the existence of the water-metal ion bridge, confirm that the serine and glutamic acid residues anchor the bridge, demonstrate that the bridge is the primary conduit for interactions between clinically relevant quinolones and topoisomerase IV and provide a likely mechanism for the most common causes of quinolone resistance.
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