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首页> 外文期刊>Journal of Molecular Biology >Crystal Structure of Geneticin Bound to a Bacterial 16S Ribosomal RNA A Site Oligonucleotide.
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Crystal Structure of Geneticin Bound to a Bacterial 16S Ribosomal RNA A Site Oligonucleotide.

机译：遗传霉素的晶体结构与细菌16S核糖体RNA A位点寡核苷酸结合。

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摘要

Aminoglycosides are antibacterial molecules that decrease translation accuracy by binding to the decoding aminoacyl-tRNA site (A site) on 16S ribosomal RNA. We have solved the crystal structure of an RNA fragment containing the A site bound to geneticin at 2.40A resolution. Geneticin, also known as G418, is a gentamicin-related aminoglycoside: it contains three rings that are functionalized by hydroxyl, ammonium and methyl groups. The detailed comparison of the distinctive behaviour of geneticin (binding to pro- and eukaryotic A sites) with the crystallographic, biochemical and microbiological results obtained so far for aminoglycoside-A site complexes offers new insights on the system. The two sugar rings constituting the neamine part common to most of the aminoglycosides bind to the A site, as already observed in the crystal structures solved previously with paromomycin and tobramycin. The essential hydrogen bonds involving ring I (to A1408) and ring II (to the phosphate oxygen atoms of the bulged adenine bases 1492 and 1493 and to G1494) are conserved and additional contacts are observed from ring III (to phosphate oxygen atoms of G1405 and U1406). The present work illustrates a molecular basis of the range in sensitiveness exhibited by geneticin towards common point A site mutations associated to resistance phenotypes. In addition, analysis and comparisons of the structures cast light on the role played by the conserved U1406.U1495 pair in the recognition of the A site by aminoglycosides.
机译：氨基糖苷类是通过与16S核糖体RNA上的解码氨酰基tRNA位点（A位点）结合而降低翻译准确性的抗菌分子。我们已经解决了一个RNA片段的晶体结构，该片段包含一个以2.40A的分辨率与遗传霉素结合的A位点。遗传霉素，也称为G418，是一种与庆大霉素相关的氨基糖苷：它含有三个被羟基，铵和甲基官能化的环。遗传霉素（结合到原核和真核A位点）的独特行为与迄今为止获得的氨基糖苷A位点复合物的晶体学，生化和微生物学结果的详细比较为系统提供了新的见解。如在先前用巴龙霉素和妥布霉素解析的晶体结构中已经观察到的，构成大多数氨基糖苷共有的神经胺部分的两个糖环与A位点结合。保留了涉及环I（与A1408相连）和环II（与凸出的腺嘌呤碱基1492和1493的磷酸氧原子以及与G1494相连）的基本氢键，并且从环III（与G1405和P1405的磷酸氧原子相连）观察到了另外的接触。 U1406）。本工作说明了遗传霉素对与抗性表型有关的共同点A位点突变所表现出的敏感性范围的分子基础。此外，结构的分析和比较阐明了保守的U1406.U1495对在氨基糖苷识别A位点中的作用。

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