Structural basis for the antibiotic activity of ketolides and azalides
Structural basis for the antibiotic activity of ketolides and azalides
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DOI：
10.1016/s0969-2126(03)00022-4
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发表时间：
2003-03-01
期刊：
影响因子：
5.7
通讯作者：
Yonath, A
中科院分区：
文献类型：
--
作者：
Schlünzen, F;Harms, JM;Yonath, A
氮杂内酯阿奇霉素和酮内酯ABT-773，这是由红霉素的化学修饰，表现出对青霉素和大环内酯耐药致病菌的数量升高的活性。与阿奇霉素或ABT-773复合的耐辐射球菌的大核糖体亚基的晶体结构的分析表明，尽管它们与核糖体接触的数量和性质不同，但这两种化合物都通过阻断蛋白质出口通道来发挥其抗微生物活性。与迄今为止研究的所有大环内酯相反，阿奇霉素的两个分子同时结合到隧道。另外的分子还与两种蛋白质L4和L22相互作用，这两种蛋白质与大环内酯类耐药性有关。这些研究阐明并合理化了药物对特定大环内酯类耐药细菌的增强活性。
The azalide azithromycin and the ketolide ABT-773, which were derived by chemical modifications of erythromycin, exhibit elevated activity against a number of penicillin- and macrolide-resistant pathogenic bacteria. Analysis of the crystal structures of the large ribosomal subunit from Deinococcus radiodurans complexed with azithromycin or ABT-773 indicates that, despite differences in the number and nature of their contacts with the ribosome, both compounds exert their antimicrobial activity by blocking the protein exit tunnel. In contrast to all macrolides studied so far, two molecules of azithromycin bind simultaneously to the tunnel. The additional molecule also interacts with two proteins, L4 and L22, implicated in macrolide resistance. These studies illuminated and rationalized the enhanced activity of the drugs against specific macrolide-resistant bacteria.