ArticleJournal of molecular biology2009
Asp-to-Asn substitution at the first position of the DxD TOPRIM motif of recombinant bacterial topoisomerase I is extremely lethal to E. coli.
Article in Journal of molecular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- Search for Specific Inhibitors Targeting Type IA Topoisomerases.Journal of molecular biology · 2026Review
- Insights into the DNA and RNA Interactions of Human Topoisomerase III Beta Using Molecular Dynamics Simulations.Journal of chemical information and modeling · 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
- 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
- Article
- Investigating mycobacterial topoisomerase I mechanism from the analysis of metal and DNA substrate interactions at the active site.Nucleic acids research · 2018Article
- RNA topoisomerase is prevalent in all domains of life and associates with polyribosomes in animals.Nucleic acids research · 2016Article
- 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
- Inhibition of Zn(II) binding type IA topoisomerases by organomercury compounds and Hg(II).PloS one · 2015Article
- Metal ion and inter-domain interactions as functional networks in E. coli topoisomerase I.Gene · 2013Article
- Single nucleotide polymorphisms of mucosa-associated lymphoid tissue 1 in oral carcinoma cells and gingival fibroblasts.Odontology · 2013Article
- Identification of anziaic acid, a lichen depside from Hypotrachyna sp., as a new topoisomerase poison inhibitor.PloS one · 2013Article
- Resistance to topoisomerase cleavage complex induced lethality in Escherichia coli via titration of transcription regulators PurR and FNR.BMC microbiology · 2011Article
- All tangled up: how cells direct, manage and exploit topoisomerase function.Nature reviews. Molecular cell biology · 2011Review
- Topoisomerase I function during Escherichia coli response to antibiotics and stress enhances cell killing from stabilization of its cleavage complex.The Journal of antimicrobial chemotherapy · 2011Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The TOPRIM domain found in many nucleotidyl transferases contains a DxD motif involved in magnesium ion coordination for catalysis. Medium- to high-copy-number plasmid clones of Yersinia pestis topoisomerase I (YpTOP) with Asp-to-Asn substitution at the first aspartate residue (D117N) of this motif could not be generated in Escherichia coli without second-site mutation even when expression was under the control of the tightly regulated BAD promoter and suppressed by 2% glucose in the medium. Arabinose induction of a single-copy YpTOP-D117N mutant gene integrated into the chromosome resulted in approximately 10(5)-fold of cell killing in 2.5 h. Attempt to induce expression of the corresponding E. coli topoisomerase I mutant (EcTOP-D111N) encoded on a high-copy-number plasmid resulted in either loss of viability or reversion of the clone to wild type. High-copy-number plasmid clones of YpTOP-D119N and EcTOP-D113N with the Asn substitution at the second Asp of the TOPRIM motif could be stably maintained, but overexpression also decreased cell viability significantly. The Asp-to-Asn substitutions at these TOPRIM residues can selectively decrease Mg(2+) binding affinity with minimal disruption of the active-site geometry, leading to trapping of the covalent complex with cleaved DNA and causing bacterial cell death. The extreme sensitivity of the first TOPRIM position suggested that this might be a useful site for binding of small molecules that could act as topoisomerase poisons.
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Registered trials
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