ArticleNucleic acids research2011
Use of divalent metal ions in the DNA cleavage reaction of topoisomerase IV.
Article in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- 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
- Cryo-EM structures of the Spo11 core complex bound to DNA.Nature structural & molecular biology · 2025Article
- Reconstitution of SPO11-dependent double-strand break formation.bioRxiv : the preprint server for biology · 2024Article
- 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
- Gyrase and Topoisomerase IV: Recycling Old Targets for New Antibacterials to Combat Fluoroquinolone Resistance.ACS infectious diseases · 2024Review
- Interactions between Gepotidacin andACS infectious diseases · 2024Article
- Cryo-EM structure of the Spo11 core complex bound to DNA.bioRxiv : the preprint server for biology · 2023Article
- Telling Your Right Hand from Your Left: The Effects of DNA Supercoil Handedness on the Actions of Type II Topoisomerases.International journal of molecular sciences · 2023Review
- Structural and biochemical basis for DNA and RNA catalysis by human Topoisomerase 3β.Nature communications · 2022Article
- Bimodal Actions of a Naphthyridone/Aminopiperidine-Based Antibacterial That Targets Gyrase and Topoisomerase IV.Biochemistry · 2019Article
- A new class of antibacterials, the imidazopyrazinones, reveal structural transitions involved in DNA gyrase poisoning and mechanisms of resistance.Nucleic acids research · 2018Article
- Topoisomerases as anticancer targets.The Biochemical journal · 2018Review
- Calcium-driven DNA synthesis by a high-fidelity DNA polymerase.Nucleic acids research · 2017Article
- Interactions between Quinolones and Bacillus anthracis Gyrase and the Basis of Drug Resistance.Biochemistry · 2017Article
- The Current Case of Quinolones: Synthetic Approaches and Antibacterial Activity.Molecules (Basel, Switzerland) · 2016Review
- Fluoroquinolones stimulate the DNA cleavage activity of topoisomerase IV by promoting the binding of Mg(2+) to the second metal binding site.Biochimica et biophysica acta · 2016Article
- Bypassing fluoroquinolone resistance with quinazolinediones: studies of drug-gyrase-DNA complexes having implications for drug design.ACS chemical biology · 2014Article
- Mechanism of quinolone action and resistance.Biochemistry · 2014Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
It has long been known that type II topoisomerases require divalent metal ions in order to cleave DNA. Kinetic, mutagenesis and structural studies indicate that the eukaryotic enzymes utilize a novel variant of the canonical two-metal-ion mechanism to promote DNA scission. However, the role of metal ions in the cleavage reaction mediated by bacterial type II enzymes has been controversial. Therefore, to resolve this critical issue, this study characterized the DNA cleavage reaction of Escherichia coli topoisomerase IV. We utilized a series of divalent metal ions with varying thiophilicities in conjunction with oligonucleotides that replaced bridging and non-bridging oxygen atoms at (and near) the scissile bond with sulfur atoms. DNA scission was enhanced when thiophilic metal ions were used with substrates that contained bridging sulfur atoms. In addition, the metal-ion dependence of DNA cleavage was sigmoidal in nature, and rates and levels of DNA cleavage increased when metal ion mixtures were used in reactions. Based on these findings, we propose that topoisomerase IV cleaves DNA using a two-metal-ion mechanism in which one of the metal ions makes a critical interaction with the 3'-bridging atom of the scissile phosphate and facilitates DNA scission by the bacterial type II enzyme.
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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.