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利用细菌 DNA 拓扑异构酶作为药物靶点:现状与展望。

Exploiting bacterial DNA gyrase as a drug target: current state and perspectives.

机构信息

Department Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK.

出版信息

Appl Microbiol Biotechnol. 2011 Nov;92(3):479-97. doi: 10.1007/s00253-011-3557-z. Epub 2011 Sep 9.

Abstract

DNA gyrase is a type II topoisomerase that can introduce negative supercoils into DNA at the expense of ATP hydrolysis. It is essential in all bacteria but absent from higher eukaryotes, making it an attractive target for antibacterials. The fluoroquinolones are examples of very successful gyrase-targeted drugs, but the rise in bacterial resistance to these agents means that we not only need to seek new compounds, but also new modes of inhibition of this enzyme. We review known gyrase-specific drugs and toxins and assess the prospects for developing new antibacterials targeted to this enzyme.

摘要

DNA 回旋酶是一种 II 型拓扑异构酶,它可以在 ATP 水解的情况下将负超螺旋引入 DNA。它在所有细菌中都是必不可少的,但在高等真核生物中却不存在,这使其成为抗菌药物的一个有吸引力的靶点。氟喹诺酮类药物就是非常成功的靶向回旋酶的药物的例子,但细菌对这些药物的耐药性不断上升,这意味着我们不仅需要寻找新的化合物,还需要寻找抑制这种酶的新方法。我们回顾了已知的回旋酶特异性药物和毒素,并评估了针对这种酶开发新抗菌药物的前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5979/3189412/784c8cf8e027/253_2011_3557_Fig1_HTML.jpg

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