Aminoglycoside binding to human and bacterial A-Site rRNA decoding region constructs.
Aminoglycoside binding to human and bacterial A-Site rRNA decoding region constructs.
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DOI：
10.1016/s0968-0896(01)00034-7
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发表时间：
2001-10
影响因子：
3.5
通讯作者：
D. Ryu;Robert R. Rando
中科院分区：
文献类型：
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作者：
D. Ryu;Robert R. Rando
16S细菌核糖体A位编码rRNA区域被认为是氨基糖苷类抗生素的药理靶点。氨基糖苷类药物的临床应用可能取决于这些药物与原核生物的A位点的结合优势，而不是真核细胞中相应的A位点。然而，本文报道的在原核和真核A位RNA结构上的氨基糖苷类定量结合实验表明，氨基糖苷类化合物与这两个靶标的结合亲和力几乎不同。在新霉素的情况下，亲和力的最大差异是4倍，原核A位结构显示出更高的结合亲和力。突变研究表明，解码区构建了非沃森-克里克(WC)碱基配对的保留元件，与μM范围内的氨基糖苷类化合物特异性结合。这些研究与氨基糖苷类抗生素可以与RNA分子特异性结合的观点一致，只要后者具有非A型结构元件，允许氨基糖苷类抗生素进入狭窄的主槽。
The 16S bacterial ribosomal A-site decoding rRNA region is thought to be the pharmacological target for the aminoglycoside antibiotics. The clinical utility of aminoglycosides could possibly depend on the preferential binding of these drugs to the prokaryotic A-site versus the corresponding A-site from eukaryotes. However, quantitative aminoglycoside binding experiments reported here on prokaryotic and eukaryotic A-site RNA constructs show that there is little in the way of differential binding affinities of aminoglycosides for the two targets. The largest difference in affinity is 4-fold in the case of neomycin, with the prokaryotic A-site construct exhibiting the higher binding affinity. Mutational studies revealed that decoding region constructs retaining elements of non-Watson–Crick (WC) base pairing, specifically bound aminoglycosides with affinities in the μM range. These studies are consistent with the idea that aminoglycoside antibiotics can specifically bind to RNA molecules as long as the latter have non-A form structural elements allowing access of aminoglycosides to the narrow major groove.