Exploiting bacterial DNA gyrase as a drug target: current state and perspectives.
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TLDR
Known gyrase-specific drugs and toxins are reviewed and the prospects for developing new antibacterials targeted to this enzyme are assessed.Abstract:
DNA gyrase is a type II topoisomerase that can introduce negative supercoils into DNA at the expense of ATP hydrolysis. It is essential in all bacteria but absent from higher eukaryotes, making it an attractive target for antibacterials. The fluoroquinolones are examples of very successful gyrase-targeted drugs, but the rise in bacterial resistance to these agents means that we not only need to seek new compounds, but also new modes of inhibition of this enzyme. We review known gyrase-specific drugs and toxins and assess the prospects for developing new antibacterials targeted to this enzyme.read more
Citations
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Structure-based discovery of substituted 4,5'-bithiazoles as novel DNA gyrase inhibitors.
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YcaO-Dependent Posttranslational Amide Activation: Biosynthesis, Structure, and Function
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References
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The Phytotoxin Albicidin is a Novel Inhibitor of DNA Gyrase
TL;DR: This work shows that albicidin is a potent inhibitor of the supercoiling activity of bacterial and plant DNA gyrases, with 50% inhibitory concentrations less than those of most coumarins and quinolones, and indicates the potential for the development of new antibacterial drugs.
Journal ArticleDOI
A Crystal Structure of the Bifunctional Antibiotic Simocyclinone D8, Bound to DNA Gyrase
Marcus J. Edwards,Ruth H. Flatman,Lesley A. Mitchenall,Clare E. M. Stevenson,Tung B. K. Le,Thomas A. Clarke,Adam R. McKay,Hans-Peter Fiedler,Mark J. Buttner,David M. Lawson,Anthony Maxwell +10 more
TL;DR: The crystal structure of the complex formed between the N-terminal domain of the Escherichia coli gyrase A subunit and simocyclinone D8 is reported, revealing two binding pockets that separately accommodate the aminocoumarin and polyketide moieties of the antibiotic.
Journal ArticleDOI
Plasmid RK2 toxin protein ParE: purification and interaction with the ParD antitoxin protein.
TL;DR: The results of glutathione-agarose affinity binding and glutaraldehyde cross-linking indicate that ParE' exists as a dimer in solution and that it binds to the dimeric form of ParD to form a tetrameric complex.
Journal ArticleDOI
Preliminary characterization of an antibiotic produced by Xanthomonas albilineans which inhibits DNA synthesis in Escherichia coli.
Robert G. Birch,Suresh S. Patil +1 more
TL;DR: Chlorosis-inducing isolates of Xanthomonas albilineans, the sugarcane leaf scald pathogen, produced a mixture of antibacterial compounds in culture that showed no cross-resistance between albicidin and inhibitors of either subunit of DNA gyrase.
Journal ArticleDOI
The DNA replication inhibitor microcin B17 is a forty-three-amino-acid protein containing sixty percent glycine
TL;DR: The N‐terminal amino acid sequence and amino acid composition demonstrated that mcbA is the structural gene for microcin B17, a low‐molecular‐weight protein that inhibits DNA replication in a number of enteric bacteria.
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