ArticleThe Journal of biological chemistry2005
Bacterial cell killing mediated by topoisomerase I DNA cleavage activity.
Article in The Journal of biological chemistry, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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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
38 citing papers in PubMed, 57 citations in OpenAlex.
- Search for Specific Inhibitors Targeting Type IA Topoisomerases.Journal of molecular biology · 2026Review
- Interactions between Gepotidacin andACS infectious diseases · 2024Article
- TOP3A coupling with replication forks and repair of TOP3A cleavage complexes.Cell cycle (Georgetown, Tex.) · 2024Review
- Replication-associated formation and repair of human topoisomerase IIIα cleavage complexes.Nature communications · 2023Article
- Exonuclease VII repairs quinolone-induced damage by resolving DNA gyrase cleavage complexes.Science advances · 2021Article
- Type IA Topoisomerases as Targets for Infectious Disease Treatments.Microorganisms · 2021Review
- DNA and RNA Cleavage Complexes and Repair Pathway for TOP3B RNA- and DNA-Protein Crosslinks.Cell reports · 2020Article
- Rapid, direct detection of bacterial topoisomerase 1-DNA adducts by RADAR/ELISA.Analytical biochemistry · 2020Article
- Mechanism of Type IA Topoisomerases.Molecules (Basel, Switzerland) · 2020Review
- Covalent Complex of DNA and Bacterial Topoisomerase: Implications in Antibacterial Drug Development.ChemMedChem · 2020Article
- Small Molecule Condensin Inhibitors.ACS infectious diseases · 2018Article
- Discovery of novel bacterial topoisomerase I inhibitors by use of in silico docking and in vitro assays.Scientific reports · 2018Article
- Deacetylation of topoisomerase I is an important physiological function of E. coli CobB.Nucleic acids research · 2017Article
- Structural basis for suppression of hypernegative DNA supercoiling by E. coli topoisomerase I.Nucleic acids research · 2015Article
- An endogenous protein inhibitor, YjhX (TopAI), for topoisomerase I from Escherichia coli.Nucleic acids research · 2015Article
- Antimicrobial Susceptibility and SOS-Dependent Increase in Mutation Frequency Are Impacted by Escherichia coli Topoisomerase I C-Terminal Point Mutation.Antimicrobial agents and chemotherapy · 2015Article
- Use of double-stranded DNA mini-circles to characterize the covalent topoisomerase-DNA complex.Scientific reports · 2015Article
- Targeting bacterial topoisomerase I to meet the challenge of finding new antibiotics.Future medicinal chemistry · 2015Review
- Changes in lipid distribution in E. coli strains in response to norfloxacin.Journal of mass spectrometry : JMS · 2015Article
- Inhibition of Zn(II) binding type IA topoisomerases by organomercury compounds and Hg(II).PloS one · 2015Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
DNA topoisomerases are important clinical targets for antibacterial and anticancer therapy. At least one type IA DNA topoisomerase can be found in every bacterium, making it a logical target for antibacterial agents that can convert the enzyme into poison by trapping its covalent complex with DNA. However, it has not been possible previously to observe the consequence of having such a stabilized covalent complex of bacterial topoisomerase I in vivo. We isolated a mutant of recombinant Yersinia pestis topoisomerase I that forms a stabilized covalent complex with DNA by screening for the ability to induce the SOS response in Escherichia coli. Overexpression of this mutant topoisomerase I resulted in bacterial cell death. From sequence analysis and site-directed mutagenesis, it was determined that a single amino acid substitution in the TOPRIM domain changing a strictly conserved glycine residue to serine in either the Y. pestis or E. coli topoisomerase I can result in a mutant enzyme that has the SOS-inducing and cell-killing properties. Analysis of the purified mutant enzymes showed that they have no relaxation activity but retain the ability to cleave DNA and form a covalent complex. These results demonstrate that perturbation of the active site region of bacterial topoisomerase I can result in stabilization of the covalent intermediate, with the in vivo consequence of bacterial cell death. Small molecules that induce similar perturbation in the enzyme-DNA complex should be candidates as leads for novel antibacterial agents.
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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.