Binding of neomycin-class aminoglycoside antibiotics to the A-site of 16 S rRNA
Binding of neomycin-class aminoglycoside antibiotics to the A-site of 16 S rRNA
复制标题
DOI：
10.1006/jmbi.1997.1552
复制
发表时间：
1998-03-27
影响因子：
5.6
通讯作者：
Puglisi, JD
中科院分区：
文献类型：
--
作者：
Fourmy, D;Recht, MI;Puglisi, JD
氨基糖苷类抗生素在氨基酰基trna位点（a位点）与核糖体RNA结合，导致遗传密码误读并抑制易位。我们最近解决了A-site RNA-paromomycin复合物的结构。该结构表明，环I和环II是所有与a位点结合的氨基糖苷所共有的，是特定核糖体结合影响翻译的最小基序。这一假设得到了生化检验，并对氨基糖苷类帕罗霉素、新霉素、核糖素和奈米胺与a位点RNA的相互作用进行了详细的核磁共振对比研究。我们的核磁共振数据显示，新霉素类氨基糖苷的I和II环足以赋予抗生素与模型a位点RNA结合的特异性。新霉素、帕罗霉素、核糖素和奈米胺结合在a位点RNA的主要凹槽中，形成一个独特的结合袋，由非规范碱基对和一个凸起的核苷酸形成。与新霉素、帕罗霉素、核糖素和奈胺形成的不同配合物中RNA的相似NMR性质和不同抗生素表明这些配合物的结构相似。(C) 1998学术出版社有限公司
Aminoglycoside antibiotics that bind to ribosomal RNA in the aminoacyl-tRNA site (A-site) cause misreading of the genetic code and inhibit translocation. We have recently solved the structure of an A-site RNA-paromomycin complex. The structure suggested that rings I and II, common to all aminoglycosides that bind to the A-site, are the minimum motif for specific ribosome binding to affect translation. This hypothesis was tested biochemically and with a detailed comparative NMR study of interaction of the aminoglycosides paromomycin, neomycin, ribostamycin, and neamine with the A-site RNA. Our NMR data show that rings I and II of neomycin-class aminoglycosides are sufficient to confer specificity to the binding of the antibiotics to the model A-site RNA. Neomycin, paromomycin, ribostamycin and neamine bind in the major groove of the A-site RNA in a unique binding pocket formed by non-canonical base pairs and a bulged nucleotide. Similar NMR properties of the RNA and the diverse antibiotics within the different complexes formed with neomycin, paromomycin, ribostamycin and neamine suggest similar structures for these complexes. (C) 1998 Academic Press Limited.