Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria
Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria
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DOI：
10.1038/35101544
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发表时间：
2001-10-25
期刊：
影响因子：
64.8
通讯作者：
Franceschi, F
中科院分区：
文献类型：
--
作者：
Schlünzen, F;Zarivach, R;Franceschi, F
核糖体是蛋白质合成的部位，是天然和合成抗生素的主要靶点。抗生素结合位点的详细知识是理解药物作用机制的核心。相反，药物是研究核糖体功能的极好工具。为了阐明核糖体-抗生素相互作用的结构基础，我们测定了耐辐射球菌真细菌50S核糖体亚基的高分辨率x射线结构，并与临床相关的抗生素氯霉素、克林霉素和三种大环内酯类红霉素、克拉霉素和罗红霉素配合。我们发现抗生素结合位点完全由肽基转移酶腔的23S核糖体RNA片段组成，并且不涉及药物与核糖体蛋白的任何相互作用。在这里，我们报告了抗生素与其结合位点的成分相互作用的细节。我们的结果还显示了假定的Mg+2离子对某些药物结合的重要性。这种结构分析有助于合理的药物设计。
Ribosomes, the site of protein synthesis, are a major target for natural and synthetic antibiotics. Detailed knowledge of antibiotic binding sites is central to understanding the mechanisms of drug action. Conversely, drugs are excellent tools for studying the ribosome function. To elucidate the structural basis of ribosome-antibiotic interactions, we determined the high-resolution X-ray structures of the 50S ribosomal subunit of the eubacterium Deinococcus radiodurans, complexed with the clinically relevant antibiotics chloramphenicol, clindamycin and the three macrolides erythromycin, clarithromycin and roxithromycin. We found that antibiotic binding sites are composed exclusively of segments of 23S ribosomal RNA at the peptidyl transferase cavity and do not involve any interaction of the drugs with ribosomal proteins. Here we report the details fo antibiotic interactions with the components of their binding sites. Our results also show the importance of putative Mg+2 ions for the binding of some drugs. This structural analysis should facilitate rational drug design.