ArticleProceedings of the National Academy of Sciences of the United States of America2011
Crystal structure of a covalent intermediate in DNA cleavage and rejoining by Escherichia coli DNA topoisomerase I.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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48 citing papers in PubMed, 78 citations in OpenAlex.
- Networked salt-bridges mediate magnesium-dependent conformational dynamics and functional regulation in type IA topoisomerases.Nature communications · 2026Article
- Investigation of potential hinge region forbioRxiv : the preprint server for biology · 2026Article
- DNA topoisomerase I acts as supercoiling sensor for bacterial transcription elongation.Nature structural & molecular biology · 2026Article
- The SWIB domain-containing DNA topoisomerase I ofJournal of bacteriology · 2025Article
- 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
- 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
- Article
- Archaea: A Gold Mine for Topoisomerase Diversity.Frontiers in microbiology · 2021Review
- Type IA Topoisomerases as Targets for Infectious Disease Treatments.Microorganisms · 2021Review
- Mechanism of Type IA Topoisomerases.Molecules (Basel, Switzerland) · 2020Review
- The many lives of type IA topoisomerases.The Journal of biological chemistry · 2020Review
- Mechanistic insights from structure of Mycobacterium smegmatis topoisomerase I with ssDNA bound to both N- and C-terminal domains.Nucleic acids research · 2020Article
- Covalent Complex of DNA and Bacterial Topoisomerase: Implications in Antibacterial Drug Development.ChemMedChem · 2020Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
DNA topoisomerases control DNA topology by breaking and rejoining DNA strands via covalent complexes with cleaved DNA substrate as catalytic intermediates. Here we report the structure of Escherichia coli topoisomerase I catalytic domain (residues 2-695) in covalent complex with a cleaved single-stranded oligonucleotide substrate, refined to 2.3-Å resolution. The enzyme-substrate intermediate formed after strand cleavage was captured due to the presence of the D111N mutation. This structure of the covalent topoisomerase-DNA intermediate, previously elusive for type IA topoisomerases, shows distinct conformational changes from the structure of the enzyme without bound DNA and provides detailed understanding of the covalent catalysis required for strand cleavage to take place. The portion of cleaved DNA 5' to the site of cleavage is anchored tightly with extensive noncovalent protein-DNA interactions as predicted by the "enzyme-bridged" model. Distortion of the scissile strand at the -4 position 5' to the cleavage site allows specific selectivity of a cytosine base in the binding pocket. Many antibacterial and anticancer drugs initiate cell killing by trapping the covalent complexes formed by topoisomerases. We have demonstrated in previous mutagenesis studies that accumulation of the covalent complex of bacterial topoisomerase I is bactericidal. This structure of the covalent intermediate provides the basis for the design of novel antibiotics that can trap the enzyme after formation of the covalent complex.
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