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The Interaction of Drugs with DNA Gyrase: A Model for the Molecular Basis of Quinolone Action

2000; Taylor & Francis; Volume: 19; Issue: 8 Linguagem: Inglês

10.1080/15257770008033048

1532-2335

Jonathan G. Heddle, Faye M. Barnard, Lois M. Wentzell, Anthony Maxwell,

Synthesis and biological activity

Abstract 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.