ArticleNucleic acids research2018
Investigating mycobacterial topoisomerase I mechanism from the analysis of metal and DNA substrate interactions at the active site.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- New Insights into Binding of G-segment DNA to the Active Site of Escherichia coli Topoisomerase III.Scientific reports · 2026Article
- Investigation of potential hinge region forbioRxiv : the preprint server for biology · 2026Article
- Molecular dynamics simulations reveal DNA gate opening mechanisms for M. smegmatis topoisomerase 1A.Biophysical journal · 2026Article
- Inhibition of DNA cleavage and strand passage activities of Mycobacterium tuberculosis topoisomerase I.Nucleic acids research · 2025Article
- Structural insights into human topoisomerase 3β DNA and RNA catalysis and nucleic acid gate dynamics.Nature communications · 2025Article
- Substrate binding of human and bacterial type IA topoisomerase: An experimentation with AlphaFold 3.0.Computational and structural biotechnology journal · 2025Article
- Small Molecule Inhibitors ofInternational journal of molecular sciences · 2024Article
- Insights into the DNA and RNA Interactions of Human Topoisomerase III Beta Using Molecular Dynamics Simulations.Journal of chemical information and modeling · 2024Article
- Variation of Structure and Cellular Functions of Type IA Topoisomerases across the Tree of Life.Cells · 2024Review
- What's on the Other Side of the Gate: A Structural Perspective on DNA Gate Opening of Type IA and IIA DNA Topoisomerases.International journal of molecular sciences · 2023Review
- The interaction between transport-segment DNA and topoisomerase IA-crystal structure of MtbTOP1 in complex with both G- and T-segments.Nucleic acids research · 2023Article
- Structural and biochemical basis for DNA and RNA catalysis by human Topoisomerase 3β.Nature communications · 2022Article
- Microbial Type IA Topoisomerase C-Terminal Domain Sequence Motifs, Distribution and Combination.International journal of molecular sciences · 2022Article
- Structural insights into the catalytic and inhibitory mechanisms of the flavin transferase FmnB inMedComm · 2022Article
- Structural studies of RNase M5 reveal two-metal-ion supported two-step dsRNA cleavage for 5S rRNA maturation.RNA biology · 2021Article
- 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
- Rapid, direct detection of bacterial topoisomerase 1-DNA adducts by RADAR/ELISA.Analytical biochemistry · 2020Article
- Mechanism of Type IA Topoisomerases.Molecules (Basel, Switzerland) · 2020Review
- Mechanistic insights from structure of Mycobacterium smegmatis topoisomerase I with ssDNA bound to both N- and C-terminal domains.Nucleic acids research · 2020Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
We have obtained new crystal structures of Mycobacterium tuberculosis topoisomerase I, including structures with ssDNA substrate bound to the active site, with and without Mg2+ ion present. Significant enzyme conformational changes upon DNA binding place the catalytic tyrosine in a pre-transition state position for cleavage of a specific phosphodiester linkage. Meanwhile, the enzyme/DNA complex with bound Mg2+ ion may represent the post-transition state for religation in the enzyme's multiple-step DNA relaxation catalytic cycle. The first observation of Mg2+ ion coordinated with the TOPRIM residues and DNA phosphate in a type IA topoisomerase active site allows assignment of likely catalytic role for the metal and draws a comparison to the proposed mechanism for type IIA topoisomerases. The critical function of a strictly conserved glutamic acid in the DNA cleavage step was assessed through site-directed mutagenesis. The functions assigned to the observed Mg2+ ion can account for the metal requirement for DNA rejoining but not DNA cleavage by type IA topoisomerases. This work provides new structural insights into a more stringent requirement for DNA rejoining versus cleavage in the catalytic cycle of this essential enzyme, and further establishes the potential for selective interference of DNA rejoining by this validated TB drug target.
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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.