Hoshino K, Kitamura A, Morrissey I, Sato K, Kato J, Ikeda H
Exploratory Research Laboratories I, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Antimicrob Agents Chemother. 1994 Nov;38(11):2623-7. doi: 10.1128/AAC.38.11.2623.
In order to examine the inhibitory activities of quinolones against topoisomerase IV, both subunits of this enzyme, ParC and ParE, were purified from Escherichia coli. The specific activity of topoisomerase IV decatenation was found to be more than five times greater than that of topoisomerase IV relaxation. Thus, the decatenation activity of topoisomerase IV seems the most relevant activity for use in studies of drug inhibition of this enzyme. Although topoisomerase IV was less sensitive to quinolones than DNA gyrase, the 50% inhibitory concentrations for decatenation were significantly lower than those for type I topoisomerases. Moreover, there was a positive correlation between the inhibitory activity against topoisomerase IV decatenation and that for DNA gyrase supercoiling. These results imply that topoisomerase IV could be a target for the quinolones in intact bacteria and that quinolones could inhibit not only supercoiling of DNA gyrase but also decatenation of topoisomerase IV when high concentrations of drug exist in bacterial cells.
为了检测喹诺酮类药物对拓扑异构酶IV的抑制活性，该酶的两个亚基ParC和ParE从大肠杆菌中纯化出来。发现拓扑异构酶IV解连环的比活性比其松弛活性高出五倍多。因此，拓扑异构酶IV的解连环活性似乎是用于该酶药物抑制研究的最相关活性。尽管拓扑异构酶IV对喹诺酮类药物的敏感性低于DNA促旋酶，但解连环的50%抑制浓度显著低于I型拓扑异构酶。此外，对拓扑异构酶IV解连环的抑制活性与对DNA促旋酶超螺旋的抑制活性之间存在正相关。这些结果表明，拓扑异构酶IV可能是完整细菌中喹诺酮类药物的作用靶点，并且当细菌细胞中存在高浓度药物时，喹诺酮类药物不仅可以抑制DNA促旋酶的超螺旋，还可以抑制拓扑异构酶IV的解连环。
