ArticleJournal of molecular biology2014
A new crystal structure of the bifunctional antibiotic simocyclinone D8 bound to DNA gyrase gives fresh insight into the mechanism of inhibition.
Article in Journal of molecular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 45 citations in OpenAlex.
- Recent advancements in the development of next-generation dual-targeting antibacterial agents.RSC medicinal chemistry · 2025Review
- Different propensities for gate opening in gyrases and topoisomerase IV.Nucleic acids research · 2025Article
- Article
- Whole genome analysis ofHeliyon · 2023Article
- Gac Is a Transcriptional Repressor of the Lyme Disease Spirochete's OspC Virulence-Associated Surface Protein.Journal of bacteriology · 2023Article
- Developments in Non-Intercalating Bacterial Topoisomerase Inhibitors: Allosteric and ATPase Inhibitors of DNA Gyrase and Topoisomerase IV.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Towards Conformation-Sensitive Inhibition of Gyrase: Implications of Mechanistic Insight for the Identification and Improvement of Inhibitors.Molecules (Basel, Switzerland) · 2021Review
- Two Decades of Successful SAR-Grounded Stories of the Novel Bacterial Topoisomerase Inhibitors (NBTIs).Journal of medicinal chemistry · 2020Review
- Novel Small Molecules against Two Binding Sites of Wnt2 Protein as potential Drug Candidates for Colorectal Cancer: A Structure Based Virtual Screening Approach.Iranian journal of pharmaceutical research : IJPR · 2020Article
- Probing structural requirements for human topoisomerase I inhibition by a novel N1-Biphenyl fluoroquinolone.European journal of medicinal chemistry · 2019Article
- Topoisomerases as anticancer targets.The Biochemical journal · 2018Review
- Structural insights into simocyclinone as an antibiotic, effector ligand and substrate.FEMS microbiology reviews · 2018Review
- Versatility of 7-Substituted Coumarin Molecules as Antimycobacterial Agents, Neuronal Enzyme Inhibitors and Neuroprotective Agents.Molecules (Basel, Switzerland) · 2017Article
- Substrate-Assisted Catalysis in Polyketide Reduction Proceeds via a Phenolate Intermediate.Cell chemical biology · 2016Article
- Topoisomerase Inhibitors: Fluoroquinolone Mechanisms of Action and Resistance.Cold Spring Harbor perspectives in medicine · 2016Review
- Molecular level understanding of resistance to nalidixic acid in Salmonella enteric serovar typhimurium associates with the S83F sequence type.European biophysics journal : EBJ · 2016Article
- Protective effect of Qnr on agents other than quinolones that target DNA gyrase.Antimicrobial agents and chemotherapy · 2015Article
- SimC7 Is a Novel NAD(P)H-Dependent Ketoreductase Essential for the Antibiotic Activity of the DNA Gyrase Inhibitor Simocyclinone.Journal of molecular biology · 2015Article
- DNA Topoisomerases.EcoSal Plus · 2015Review
- Identification of novel bacterial DNA gyrase inhibitors: An in silico study.Research in pharmaceutical sciencesArticle
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Simocyclinone D8 (SD8) is an antibiotic produced by Streptomyces antibioticus that targets DNA gyrase. A previous structure of SD8 complexed with the N-terminal domain of the DNA gyrase A protein (GyrA) suggested that four SD8 molecules stabilized a tetramer of the protein; subsequent mass spectrometry experiments suggested that a protein dimer with two symmetry-related SD8s was more likely. This work describes the structures of a further truncated form of the GyrA N-terminal domain fragment with and without SD8 bound. The structure with SD8 has the two SD8 molecules bound within the same GyrA dimer. This new structure is entirely consistent with the mutations in GyrA that confer SD8 resistance and, by comparison with a new apo structure of the GyrA N-terminal domain, reveals the likely conformation changes that occur upon SD8 binding and the detailed mechanism of SD8 inhibition of gyrase. Isothermal titration calorimetry experiments are consistent with the crystallography results and further suggest that a previously observed complex between SD8 and GyrB is ~1000-fold weaker than the interaction with GyrA.
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Registered trials
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