ArticleAntimicrobial agents and chemotherapy2005
Simocyclinone D8, an inhibitor of DNA gyrase with a novel mode of action.
Article in Antimicrobial agents and chemotherapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 113 citations in OpenAlex.
- Role of DNA Double-Strand Break Formation in Gyrase Inhibitor-Mediated Killing of Nonreplicating PersistentACS infectious diseases · 2024Article
- s-Triazine Derivatives Functionalized with Alkylating 2-Chloroethylamine Fragments as Promising Antimicrobial Agents: Inhibition of Bacterial DNA Gyrases, Molecular Docking Studies, and Antibacterial and Antifungal Activity.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Discovery and biosynthetic assessment of 'Microbial genomics · 2023Article
- Developments in Non-Intercalating Bacterial Topoisomerase Inhibitors: Allosteric and ATPase Inhibitors of DNA Gyrase and Topoisomerase IV.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Characterization of the Biosynthetic Gene Cluster and Shunt Products Yields Insights into the Biosynthesis of Balmoralmycin.Applied and environmental microbiology · 2022Article
- Albicidin, a potent DNA gyrase inhibitor with clinical potential.The Journal of antibiotics · 2019Review
- Probing structural requirements for human topoisomerase I inhibition by a novel N1-Biphenyl fluoroquinolone.European journal of medicinal chemistry · 2019Article
- The Macromolecular Machines that Duplicate the Escherichia coli Chromosome as Targets for Drug Discovery.Antibiotics (Basel, Switzerland) · 2018Review
- 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
- Targeting DNA Replication and Repair for the Development of Novel Therapeutics against Tuberculosis.Frontiers in molecular biosciences · 2017Review
- Genome-guided Investigation of Antibiotic Substances produced by Allosalinactinospora lopnorensis CA15-2(T) from Lop Nor region, China.Scientific reports · 2016Article
- Diversity of Natural Product Biosynthetic Genes in the Microbiome of the Deep Sea Sponges Inflatella pellicula, Poecillastra compressa, and Stelletta normani.Frontiers in microbiology · 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
- Transcription factor-based biosensors enlightened by the analyte.Frontiers in microbiology · 2015Review
- A new crystal structure of the bifunctional antibiotic simocyclinone D8 bound to DNA gyrase gives fresh insight into the mechanism of inhibition.Journal of molecular biology · 2014Article
- Molecular basis for the differential quinolone susceptibility of mycobacterial DNA gyrase.Antimicrobial agents and chemotherapy · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
We have characterized the interaction of a new class of antibiotics, simocyclinones, with bacterial DNA gyrase. Even though their structures include an aminocoumarin moiety, a key feature of novobiocin, coumermycin A(1), and clorobiocin, which also target gyrase, simocyclinones behave strikingly differently from these compounds. Simocyclinone D8 is a potent inhibitor of gyrase supercoiling, with a 50% inhibitory concentration lower than that of novobiocin. However, it does not competitively inhibit the DNA-independent ATPase reaction of GyrB, which is characteristic of other aminocoumarins. Simocyclinone D8 also inhibits DNA relaxation by gyrase but does not stimulate cleavage complex formation, unlike quinolones, the other major class of gyrase inhibitors; instead, it abrogates both Ca(2+)- and quinolone-induced cleavage complex formation. Binding studies suggest that simocyclinone D8 interacts with the N-terminal domain of GyrA. Taken together, our results demonstrate that simocyclinones inhibit an early step of the gyrase catalytic cycle by preventing binding of the enzyme to DNA. This is a novel mechanism for a gyrase inhibitor and presents new possibilities for antibacterial drug development.
Indexed as
Identifiers
What OpenQuestion holds
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.