ArticleBiochemistry2014
Role of the water-metal ion bridge in mediating interactions between quinolones and Escherichia coli topoisomerase IV.
Article in Biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 54 citations in OpenAlex.
- Novel Bacterial Topoisomerase Inhibitors: A New Front in an Old War.Journal of molecular biology · 2026Review
- Bacterial type II topoisomerases cleave DNA in a species-specific manner.Nucleic acids research · 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
- Structural interactions of BWC0977 with Klebsiella pneumoniae topoisomerase IV and biochemical basis of its broad-spectrum activity.Communications biology · 2025Article
- Three Dihydroquinolin-4-one Derivatives as Potential Biodiesel Additives: From the Molecular Structure to Machine Learning Approach.ACS omega · 2024Article
- Antibacterial Mechanisms and Clinical Impact of Sitafloxacin.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Highly sensitive mapping of in vitro type II topoisomerase DNA cleavage sites with SHAN-seq.Nucleic acids research · 2024Article
- Highly sensitive mapping ofbioRxiv : the preprint server for biology · 2024Article
- Interactions between Gepotidacin andACS infectious diseases · 2024Article
- Target-Mediated Fluoroquinolone Resistance inACS infectious diseases · 2024Article
- Gyrase and Topoisomerase IV: Recycling Old Targets for New Antibacterials to Combat Fluoroquinolone Resistance.ACS infectious diseases · 2024Review
- Emerging resistome diversity in clinical Vibrio cholerae strains revealing their role as potential reservoirs of antimicrobial resistance.Molecular biology reports · 2024Article
- Basis for the discrimination of supercoil handedness during DNA cleavage by human and bacterial type II topoisomerases.Nucleic acids research · 2023Article
- Role of the Water-Metal Ion Bridge in Quinolone Interactions withInternational journal of molecular sciences · 2023Article
- Recognition of DNA Supercoil Handedness during Catenation Catalyzed by Type II Topoisomerases.Biochemistry · 2022Article
- Facile synthesis and antimycobacterial activity of isoniazid, pyrazinamide and ciprofloxacin derivatives.Chemical biology & drug design · 2021Article
- Selective toxicity of antibacterial agents-still a valid concept or do we miss chances and ignore risks?Infection · 2021Review
- Quinolones: Mechanism, Lethality and Their Contributions to Antibiotic Resistance.Molecules (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Although quinolones have been in clinical use for decades, the mechanism underlying drug activity and resistance has remained elusive. However, recent studies indicate that clinically relevant quinolones interact with Bacillus anthracis (Gram-positive) topoisomerase IV through a critical water-metal ion bridge and that the most common quinolone resistance mutations decrease drug activity by disrupting this bridge. As a first step toward determining whether the water-metal ion bridge is a general mechanism of quinolone-topoisomerase interaction, we characterized drug interactions with wild-type Escherichia coli (Gram-negative) topoisomerase IV and a series of ParC enzymes with mutations (S80L, S80I, S80F, and E84K) in the predicted bridge-anchoring residues. Results strongly suggest that the water-metal ion bridge is essential for quinolone activity against E. coli topoisomerase IV. Although the bridge represents a common and critical mechanism that underlies broad-spectrum quinolone function, it appears to play different roles in B. anthracis and E. coli topoisomerase IV. The water-metal ion bridge is the most important binding contact of clinically relevant quinolones with the Gram-positive enzyme. However, it primarily acts to properly align clinically relevant quinolones with E. coli topoisomerase IV. Finally, even though ciprofloxacin is unable to increase levels of DNA cleavage mediated by several of the Ser80 and Glu84 mutant E. coli enzymes, the drug still retains the ability to inhibit the overall catalytic activity of these topoisomerase IV proteins. Inhibition parallels drug binding, suggesting that the presence of the drug in the active site is sufficient to diminish DNA relaxation rates.
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