ArticleNucleic acids research2008
Mutation adjacent to the active site tyrosine can enhance DNA cleavage and cell killing by the TOPRIM Gly to Ser mutant of bacterial topoisomerase I.
Article in Nucleic acids research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- Interaction between transcribing RNA polymerase and topoisomerase I prevents R-loop formation in E. coli.Nature communications · 2022Article
- Localization ofFrontiers in microbiology · 2022Article
- Mechanism of Type IA Topoisomerases.Molecules (Basel, Switzerland) · 2020Review
- Article
- The topoisomerase 3α zinc-finger domain T1 of Arabidopsis thaliana is required for targeting the enzyme activity to Holliday junction-like DNA repair intermediates.PLoS genetics · 2018Article
- Use of double-stranded DNA mini-circles to characterize the covalent topoisomerase-DNA complex.Scientific reports · 2015Article
- Inhibition of Zn(II) binding type IA topoisomerases by organomercury compounds and Hg(II).PloS one · 2015Article
- A highly processive topoisomerase I: studies at the single-molecule level.Nucleic acids research · 2014Article
- Identification of anziaic acid, a lichen depside from Hypotrachyna sp., as a new topoisomerase poison inhibitor.PloS one · 2013Article
- The strictly conserved Arg-321 residue in the active site of Escherichia coli topoisomerase I plays a critical role in DNA rejoining.The Journal of biological chemistry · 2011Article
- Hydroxyl radicals are involved in cell killing by the bacterial topoisomerase I cleavage complex.Journal of bacteriology · 2009Article
- Effects of magnesium and related divalent metal ions in topoisomerase structure and function.Nucleic acids research · 2009Review
- Bacterial topoisomerase I as a target for discovery of antibacterial compounds.Nucleic acids research · 2009Review
- Asp-to-Asn substitution at the first position of the DxD TOPRIM motif of recombinant bacterial topoisomerase I is extremely lethal to E. coli.Journal of molecular biology · 2009Article
- Inhibition of Mg2+ binding and DNA religation by bacterial topoisomerase I via introduction of an additional positive charge into the active site region.Nucleic acids research · 2008Article
- SOS induction by stabilized topoisomerase IA cleavage complex occurs via the RecBCD pathway.Journal of bacteriology · 2008Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The TOPRIM DXDXXG residues of type IA and II topoisomerases are involved in Mg(II) binding and the cleavage-rejoining of DNA. Mutation of the strictly conserved glycine to serine in Yersinia pestis and Escherichia coli topoisomerase I results in bacterial cell killing due to inhibition of DNA religation after DNA cleavage. In this study, all other substitutions at the TOPRIM glycine of Y. pestis topoisomerase I were examined. While the Gly to Ala substitution allowed both DNA cleavage and religation, other mutations abolished DNA cleavage. DNA cleavage activity retained by the Gly to Ser mutant could be significantly enhanced by a second mutation of the methionine residue adjacent to the active site tyrosine. Induction of mutant topoisomerase with both the TOPRIM glycine and active site region methionine mutations resulted in up to 40-fold higher cell killing rate when compared with the single TOPRIM Gly to Ser mutant. Bacterial type IA topoisomerases are potential targets for discovery of novel antibiotics. These results suggest that compounds that interact simultaneously with the TOPRIM motif and the molecular surface around the active site tyrosine could be highly efficient topoisomerase poisons through both enhancement of DNA cleavage and inhibition of DNA rejoining.
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