Bacterial topoisomerases, anti-topoisomerases, and anti-topoisomerase resistance
Bacterial topoisomerases, anti-topoisomerases, and anti-topoisomerase resistance
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DOI：
10.1086/514923
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发表时间：
1998-08-01
影响因子：
11.8
通讯作者：
Hooper, DC
中科院分区：
文献类型：
--
作者：
Hooper, DC
拓扑异构酶是控制DNA分子的相互连接和扭曲所必需的普遍存在的酶。在真细菌中发现的四种拓扑异构酶中，DNA回转酶和拓扑异构酶IV已被自然界和制药工业开发为抗菌靶点。作为一种或两种拓扑异构酶抑制剂的天然产物包括香豆素和环噻吩类，它们干扰三磷酸腺苷水解、肉桂碱、黄酮和萜类衍生物。质粒编码的细菌肽microcin B17和CcdB也能抑制DNA旋切酶。然而，喹诺酮类药物是一种合成的抗菌药物，它同时作用于DNA旋切酶和拓扑异构酶IV，具有最广泛的临床应用。喹诺酮类同系物对DNA旋切酶和拓扑异构酶IV的相对效力不同。对越来越多的耐药突变酶和酵母中同源酶的晶体结构的研究有助于我们理解这些药物与拓扑异构酶-DNA复合物的相互作用以及突变影响耐药性的方式。
Topoisomerases are ubiquitous enzymes necessary for controlling the interlinking and twisting of DNA molecules. Among the four topoisomerases identified in eubacteria, two, DNA gyrase and topoisomerase IV, have been exploited by nature and the pharmaceutical industry as antibacterial targets. Natural products that are inhibitors of one or both of these topoisomerases include the coumarin and cyclothialidine classes, which interfere with adenosine triphosphate hydrolysis, cinodine, flavones, and terpenoid derivatives. The plasmid-encoded bacterial peptides microcin B17 and CcdB also inhibit DNA gyrase. The quinolones, a synthetic class of antibacterials that act on both DNA gyrase and topoisomerase IV, have had the broadest clinical applications, however, Quinolone congeners differ in their relative potencies for DNA gyrase and topoisomerase IV. Studies of an expanding set of resistant mutant enzymes and the crystal structure of the homologous enzyme in yeast have contributed to our understanding of interactions of these drugs with topoisomerase-DNA complexes and the ways in which mutations effect resistance.