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

Overview

Journal Nucleosides Nucleotides Nucleic Acids

Specialty Biochemistry

Date 2000 Nov 30

PMID 11097055

Citations 27

Authors

J G HEDDLE

F M Barnard

L M Wentzell

A Maxwell

Affiliations

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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.

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