Mechanism of Action of the Antibiotic NXL101, a Novel Nonfluoroquinolone Inhibitor of Bacterial Type II Topoisomerases

No abstract is available for this paper.

• Publication year

  2008

• Venue

  Antimicrobial Agents and Chemotherapy

• Publication date

  2008-07-14

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1128/AAC.00496-08PMID 18625781PMCID PMC2533460
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Quinolone-Mediated Bacterial Death

  2007cited by this paper
• Energy coupling in type II topoisomerases: why do they hydrolyze ATP?

  2007cited by this paper
• Breakage-Reunion Domain of Streptococcus pneumoniae Topoisomerase IV: Crystal Structure of a Gram-Positive Quinolone Target

  2007cited by this paper
• Origin and evolution of DNA topoisomerases.

  2007cited by this paper
• Lethal fragmentation of bacterial chromosomes mediated by DNA gyrase and quinolones

  2006cited by this paper
• Role of the Extended α4 Domain of Staphylococcus aureus Gyrase A Protein in Determining Low Sensitivity to Quinolones

  2006cited by this paper
• An improved expression plasmid for affinity purification of Staphylococcus aureus gyrase A subunit.

  2006cited by this paper
• The structural basis for substrate specificity in DNA topoisomerase IV.

  2005cited by this paper
• The C-terminal domain of DNA gyrase A adopts a DNA-bending beta-pinwheel fold.

  2004cited by this paper
• The C-terminal domain of DNA gyrase A adopts a DNA-bending β-pinwheel fold

  2004cited by this paper
• Structure, molecular mechanisms, and evolutionary relationships in DNA topoisomerases.

  2004cited by this paper
• Topoisomerase Targeting with and Resistance to Gemifloxacin in Staphylococcus aureus

  2003cited by this paper
• Analysis of dual active fluoroquinolones in Streptococcus pneumoniae.

  2003cited by this paper
• The history of quinolones

  2003cited by this paper
• Activity of and Resistance to Moxifloxacin in Staphylococcus aureus

  2003cited by this paper
• Small-Colony Mutants of Staphylococcus aureus Allow Selection of Gyrase-Mediated Resistance to Dual-Target Fluoroquinolones

  2002cited by this paper
• Dual Targeting of DNA Gyrase and Topoisomerase IV: Target Interactions of Garenoxacin (BMS-284756, T-3811ME), a New Desfluoroquinolone

  2002influential reference
• Cleavable-Complex Formation by Wild-Type and Quinolone-Resistant Streptococcus pneumoniae Type II Topoisomerases Mediated by Gemifloxacin and Other Fluoroquinolones

  2002cited by this paper
• Identification of four GyrA residues involved in the DNA breakage-reunion reaction of DNA gyrase.

  2002cited by this paper
• Mutation in the DNA Gyrase A Gene ofEscherichia coli That Expands the Quinolone Resistance-Determining Region

  2001cited by this paper
• DNA topoisomerases: structure, function, and mechanism.

  2001cited by this paper
• Mechanisms of action of antimicrobials: focus on fluoroquinolones.

  2001cited by this paper
• Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically : approved standard

  2000cited by this paper
• Action of quinolones against Staphylococcus aureus topoisomerase IV: basis for DNA cleavage enhancement.

  2000cited by this paper
• Intracellular targets of moxifloxacin: a comparison with other fluoroquinolones.

  2000cited by this paper
• Potent Antipneumococcal Activity of Gemifloxacin Is Associated with Dual Targeting of Gyrase and Topoisomerase IV, an In Vivo Target Preference for Gyrase, and Enhanced Stabilization of Cleavable Complexes In Vitro

  2000cited by this paper
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  2000cited by this paper
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  1998cited by this paper
• Crystal structure of the breakage–reunion domain of DNA gyrase

  1997influential reference
• A novel, double mutation in DNA gyrase A of Escherichia coli conferring resistance to quinolone antibiotics

  1997cited by this paper
• Differential behaviors of Staphylococcus aureus and Escherichia coli type II DNA topoisomerases

  1996cited by this paper
• Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically

  1990cited by this paper
• Mapping the active site tyrosine of Escherichia coli DNA gyrase.

  1987cited by this paper
• National Committee for Clinical Laboratory Standards.

  1980cited by this paper

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  2023cites this paper
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  2022cites this paper
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  2022cites this paper
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  2022cites this paper
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  2021cites this paper
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  2021cites this paper
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  2021cites this paper
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  2020cites this paper
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  2020cites this paper
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  2020cites this paper
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  2019cites this paper
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  2019cites this paper
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  2019cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2018cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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