The interaction of drugs with DNA gyrase: a model for the molecular basis of quinolone action

Nucleosides Nucleotides Nucleic Acids. 2000 Aug;19(8):1249-64. doi: 10.1080/15257770008033048.


DNA gyrase supercoils DNA in bacteria. The fact that it is essential in all bacteria and absent from eukaryotes makes it an ideal drug target. We discuss the action of coumarin and quinolone drugs on gyrase. In the case of coumarins, the drugs are known to be competitive inhibitors of the gyrase ATPase reaction. From a combination of structural and biochemical studies, the molecular details of the gyrase-coumarin complex are well established. In the case of quinolones, the drugs are thought to act by stabilising a cleavage complex between gyrase and DNA that arrests polymerases in vivo. The exact nature of the gyrase-quinolone-DNA complex is not known; we propose a model for this complex based on structural and biochemical data.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacology
  • Bacteria / drug effects
  • Bacteria / enzymology
  • Bacterial Proteins / antagonists & inhibitors
  • Binding Sites
  • Coumarins / chemistry
  • Coumarins / pharmacology*
  • DNA / metabolism
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Macromolecular Substances
  • Models, Chemical
  • Molecular Conformation
  • Novobiocin / metabolism
  • Protein Conformation
  • Protein Structure, Tertiary
  • Protein Subunits
  • Quinolones / chemistry
  • Quinolones / pharmacology*
  • Structure-Activity Relationship
  • Topoisomerase II Inhibitors*


  • Anti-Infective Agents
  • Bacterial Proteins
  • Coumarins
  • Enzyme Inhibitors
  • Macromolecular Substances
  • Protein Subunits
  • Quinolones
  • Topoisomerase II Inhibitors
  • Novobiocin
  • DNA