Paromomycin binding induces a local conformational change in the A-site of 16 S rRNA
Paromomycin binding induces a local conformational change in the A-site of 16 S rRNA
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DOI：
10.1006/jmbi.1997.1551
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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;Yoshizawa, S;Puglisi, JD
氨基糖苷类抗生素在氨酰-tRNA位点（A位点）与核糖体RNA结合，导致遗传密码的误读并抑制易位。A位点RNA寡核苷酸特异性结合氨基糖苷类抗生素，并且RNA-巴龙霉素复合物的结构先前通过核磁共振（NMR）光谱测定。在这里，A-位点的RNA结构在其游离形式已被确定使用heterowitz NMR和巴龙霉素-RNA复合物的结构进行了比较。与巴龙霉素复合物一样，不对称内环由一个Watson-Crick碱基对（C1407.G1494）和两个非典型碱基对（U1406.U1495，A1408.A1493）闭合。A1492堆叠在A1493下面，并插入上下茎之间。比较了16 S rRNA的自由构象和结合构象，发现在抗生素存在下，16 S rRNA的A位点的两个普遍保守的残基A1492和A1493被移位到RNA螺旋的小沟上。RNA构象的这些变化将A1492和A1493的N1位置置于A位点RNA的小沟侧，并表明氨基糖苷类对翻译的作用机制。(C)出版社：Academic Press Limited。
Aminoglycoside antibiotics that bind to ribosomal RNA in the aminoacyl-tRNA site (A-site) cause misreading of the genetic code and inhibit translocation. An A-site RNA oligonucleotide specifically binds to aminoglycoside antibiotics and the structure of the RNA-paromomycin complex was previously determined by nuclear magnetic resonance (NMR) spectroscopy. Here, the A-site RNA structure in its free form has been determined using heteronuclear NMR and compared to the structure of the paromomycin-RNA complex. As in the complex with paromomycin, the asymmetric internal loop is closed by a Watson-Crick base-pair (C1407.G1494) and by two non-canonical base-pairs (U1406.U1495, A1408.A1493). A1492 stacks below A1493 and is intercalated between the upper and lower stems. The comparison of the free and bound conformations of the RNA shows that two universally conserved residues of the A site of 16 S rRNA, A1492 and A1493, are displaced towards the minor groove of the RNA helix in presence of antibiotic. These changes in the RNA conformation place the N1 positions of A1492 and A1493 on the minor groove side of the A-site RNA and suggest a mechanism of action of aminoglycosides on translation. (C) 1998 Academic Press Limited.