药物与DNA促旋酶的相互作用：喹诺酮作用分子基础的模型

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

作者信息

Heddle J G, Barnard F M, Wentzell L M, Maxwell A

机构信息

Department of Biochemistry, University of Leicester, UK.

出版信息

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

DOI:10.1080/15257770008033048

PMID:11097055

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.

摘要

DNA促旋酶可使细菌中的DNA形成超螺旋。它在所有细菌中都必不可少，而在真核生物中不存在，这一事实使其成为理想的药物靶点。我们讨论香豆素类和喹诺酮类药物对促旋酶的作用。就香豆素类药物而言，已知它们是促旋酶ATP酶反应的竞争性抑制剂。通过结构和生化研究的结合，促旋酶 - 香豆素复合物的分子细节已得到充分确立。就喹诺酮类药物而言，人们认为它们的作用方式是稳定促旋酶与DNA之间的切割复合物，从而在体内使聚合酶停滞。促旋酶 - 喹诺酮 - DNA复合物的确切性质尚不清楚；我们基于结构和生化数据提出了该复合物的模型。