Platform Technology and Science, GlaxoSmithKline, Medicines Research Centre, Stevenage, Hertfordshire, UK.
Nat Struct Mol Biol. 2010 Sep;17(9):1152-3. doi: 10.1038/nsmb.1892. Epub 2010 Aug 29.
Quinolone antibacterials have been used to treat bacterial infections for over 40 years. A crystal structure of moxifloxacin in complex with Acinetobacter baumannii topoisomerase IV now shows the wedge-shaped quinolone stacking between base pairs at the DNA cleavage site and binding conserved residues in the DNA cleavage domain through chelation of a noncatalytic magnesium ion. This provides a molecular basis for the quinolone inhibition mechanism, resistance mutations and invariant quinolone antibacterial structural features.
喹诺酮类抗菌药物已经被用于治疗细菌感染超过 40 年。莫西沙星与鲍曼不动杆菌拓扑异构酶 IV 的晶体结构显示，楔形喹诺酮类化合物堆积在 DNA 切割位点的碱基对之间，通过螯合非催化性镁离子与 DNA 切割结构域中的保守残基结合。这为喹诺酮类抑制机制、耐药突变和不变的喹诺酮类抗菌结构特征提供了分子基础。
