ArticleNucleic acids research2008
Inhibition of Mg2+ binding and DNA religation by bacterial topoisomerase I via introduction of an additional positive charge into the active site region.
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 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Unravelling the mechanisms of Type 1A topoisomerases using single-molecule approaches.Nucleic acids research · 2021Review
- Type IA Topoisomerases as Targets for Infectious Disease Treatments.Microorganisms · 2021Review
- Direct observation of topoisomerase IA gate dynamics.Nature structural & molecular biology · 2018Article
- Biochemical Basis ofInternational journal of molecular sciences · 2018Article
- Article
- 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
- Inhibition of Zn(II) binding type IA topoisomerases by organomercury compounds and Hg(II).PloS one · 2015Article
- Synthesis, structure-activity relationship studies, and antibacterial evaluation of 4-chromanones and chalcones, as well as olympicin A and derivatives.Journal of medicinal chemistry · 2014Article
- A surface plasmon resonance study of the intermolecular interaction between Escherichia coli topoisomerase I and pBAD/Thio supercoiled plasmid DNA.Biochemical and biophysical research communications · 2014Article
- Metal ion and inter-domain interactions as functional networks in E. coli topoisomerase I.Gene · 2013Article
- Identification of anziaic acid, a lichen depside from Hypotrachyna sp., as a new topoisomerase poison inhibitor.PloS one · 2013Article
- Residues of E. coli topoisomerase I conserved for interaction with a specific cytosine base to facilitate DNA cleavage.Nucleic acids research · 2012Article
- 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
- Crystal structure of a covalent intermediate in DNA cleavage and rejoining by Escherichia coli DNA topoisomerase I.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Hydroxyl radicals are involved in cell killing by the bacterial topoisomerase I cleavage complex.Journal of bacteriology · 2009Article
- Analysis of DNA relaxation and cleavage activities of recombinant Mycobacterium tuberculosis DNA topoisomerase I from a new expression and purification protocol.BMC biochemistry · 2009Article
- Bacterial topoisomerase I as a target for discovery of antibacterial compounds.Nucleic acids research · 2009Review
- Effects of magnesium and related divalent metal ions in topoisomerase structure and function.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
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Among bacterial topoisomerase I enzymes, a conserved methionine residue is found at the active site next to the nucleophilic tyrosine. Substitution of this methionine residue with arginine in recombinant Yersinia pestis topoisomerase I (YTOP) was the only substitution at this position found to induce the SOS response in Escherichia coli. Overexpression of the M326R mutant YTOP resulted in approximately 4 log loss of viability. Biochemical analysis of purified Y. pestis and E. coli mutant topoisomerase I showed that the Met to Arg substitution affected the DNA religation step of the catalytic cycle. The introduction of an additional positive charge into the active site region of the mutant E. coli topoisomerase I activity shifted the pH for optimal activity and decreased the Mg(2+) binding affinity. This study demonstrated that a substitution outside the TOPRIM motif, which binds Mg(2+)directly, can nonetheless inhibit Mg(2+) binding and DNA religation by the enzyme, increasing the accumulation of covalent cleavage complex, with bactericidal consequence. Small molecules that can inhibit Mg(2+) dependent religation by bacterial topoisomerase I specifically could be developed into useful new antibacterial compounds. This approach would be similar to the inhibition of divalent ion dependent strand transfer by HIV integrase in antiviral therapy.
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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.