Saccharide-RNA recognition in an aminoglycoside antibiotic-RNA aptamer complex
Saccharide-RNA recognition in an aminoglycoside antibiotic-RNA aptamer complex
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DOI：
10.1016/s1074-5521(97)90235-0
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发表时间：
1997-01-01
影响因子：
--
通讯作者：
Patel, DJ
中科院分区：
文献类型：
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作者：
Jiang, LC;Suri, AK;Patel, DJ
背景资料：已知氨基糖苷类抗生素以高亲和力和特异性靶向核糖体、逆转录病毒和催化RNA。最近，体外选择实验已经鉴定出RNA适体，其以纳摩尔亲和力和严格特异性结合氨基糖苷类抗生素，允许在密切相关的家族成员之间进行区分。迄今为止，关于这种糖-RNA识别的分子基础的结构信息有限。我们描述了一个解决方案，结构测定的妥布霉素-RNA适配体复合物，使用NMR和分子动力学。该结构提供了深入了解与糖RNA识别相关的分子特征。妥布霉素采用确定的比对并结合至以茎环连接位点为中心的RNA大沟。结合妥布霉素的一部分被封装之间的地板的大沟和一个环出的胞嘧啶残基，形成一个皮瓣的结合位点在complex.Conclusions：耐药病原体的出现和它们对人类健康的影响仍然是一个主要关注的医学界。合理修改现有的抗生素，旨在提高其疗效，需要从分子角度来看其受体结合位点。我们已经为靶向RNA的氨基糖苷类抗生素家族的成员提供了这样的分子视角。
Background: Aminoglycoside antibiotics are known to target ribosomal, retroviral and catalytic RNAs with high affinity and specificity, Recently, in vitro selection experiments have identified RNA aptamers that bind to aminoglycoside antibiotics with nanomolar affinity and stringent specificity, allowing discrimination between closely related family members, There has, to date, been limited structural information on the molecular basis of such saccharide-RNA recognition.Results: We describe a solution-structure determination of the tobramycin-RNA aptamer complex, obtained using NMR and molecular dynamics. The structure gives insight into the molecular features associated with saccharide-RNA recognition. Tobramycin adopts a defined alignment and binds to the RNA major groove centered about a stem-loop junction site. A portion of the bound tobramycin is encapsulated between the floor of the major groove and a looped-out cytosine residue that forms a flap over the binding site in the complex.Conclusions: The emergence of antibiotic-resistant pathogens and their impact on human health continues to be a major concern in the medical community. Rational modification of existing antibiotics aimed at improving their efficacy requires a molecular view of their receptor-binding sites. We have provided such a molecular view for a member of the aminoglycoside antibiotic family that targets RNA.