Characterization of a 1,4-disubstituted 1,2,3-triazole binding to T box antiterminator RNA.
Characterization of a 1,4-disubstituted 1,2,3-triazole binding to T box antiterminator RNA.
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1,4-二取代 1,2,3-三唑与 T 盒抗终止子 RNA 结合的表征。
DOI：
10.1016/j.bmc.2011.12.017
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发表时间：
2012
影响因子：
3.5
通讯作者：
Hines,JV
中科院分区：
文献类型：
--
作者：
Zhou,S;Means,JA;Acquaah-Harrison,G;Bergmeier,SC;Hines,JV
T盒核糖开关通过对同源的非氨基酰化(不带电)tRNA的结构反应来调节许多细菌基因的转录。核糖开关含有多个保守的RNA元件，包括一个关键的结构元件--反终止子，它与tRNA受体末端核苷酸结合。以前的研究发现，1，4-取代的1，2，3-三氮唑GHB-7可以破坏tRNA-抗终止物RNA模型复合体的形成。GHB-7与抗终止子模型RNA结合的亲和力和分子相互作用是T盒抗终止子RNA靶向药物发现项目的一部分。在线探测、紫外光监测的热变性和对接研究都一致表明，GHB-7可能与反终止子的凸起区域结合，降低了凸起核苷酸的灵活性，总体上稳定了RNA二级结构。这些结果开始阐明配体诱导抑制tRNA与T盒抗终止物RNA结合的可能机制，并有助于了解小分子如何结合相对简单的RNA结构元件，如凸起。
The T box riboswitch regulates the transcription of many bacterial genes by structurally responding to cognate non-aminoacylated (uncharged) tRNA. The riboswitch contains multiple conserved RNA elements including a key structural element, the antiterminator, which binds the tRNA acceptor end nucleotides. Previous studies identified a lead 1,4-disubstituted 1,2,3-triazole, GHB-7, that disrupted formation of a tRNA–antiterminator RNA model complex. The affinity and molecular interactions of GHB-7 binding to antiterminator model RNA were characterized as part of a comprehensive T box antiterminator RNA-targeted drug discovery project. In-line probing, UV-monitored thermal denaturation and docking studies all consistently indicated that GHB-7 likely binds to the bulge region of the antiterminator, reduces the flexibility of the bulge nucleotides and, overall, stabilizes the RNA secondary structure. These results begin to elucidate possible mechanisms for ligand-induced inhibition of tRNA binding to T box antiterminator RNA and contribute to the knowledge of how small molecules bind relatively simple RNA structural elements such as bulges.