RNA targeting through binding of small molecules: Studies on t-RNA binding by the cytotoxic protoberberine alkaloid coralyne
RNA targeting through binding of small molecules: Studies on t-RNA binding by the cytotoxic protoberberine alkaloid coralyne
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DOI：
10.1039/b816480k
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发表时间：
2009-01-01
影响因子：
--
通讯作者：
Kumar, Gopinatha Suresh
中科院分区：
文献类型：
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作者：
Islam, Md. Maidul;Pandya, Prateek;Kumar, Gopinatha Suresh
利用各种生物物理技术研究了原小檗碱生物碱coralyne与t-RNA（phe）的相互作用。吸收和荧光研究结果表明，生物碱结合t-RNA表现出积极的协同作用。等温滴定量热法结果表明，生物碱的结合主要是焓驱动与较小的有利熵项。一个令人惊讶的大的有利组件的非静电的贡献coralyne的结合到t-RNA的盐依赖性数据和解剖的自由能揭示。生物碱增强了t-RNA的热稳定性，由光学热熔融数据得到的结合亲和力值与量热法得到的结合亲和力值一致。热容量变化为-125 calmol（-1）K-1，并观察到明显的焓-熵补偿现象，证实了多个弱非共价相互作用的参与。圆二色性研究提供了证据的显着扰动的tRNA结构与伴随诱导的光学活性结合的非手性生物碱分子。从圆二色性数据产生的结合等温线证实了从光谱数据推断的生物碱的合作结合模式。对接研究提供了进一步的见解，部分插入状态的珊瑚碱内的t-RNA结构。这项研究提出了一个完整的结合和热力学过程。与t-RNA的相互作用。
Interaction of the protoberberine alkaloid coralyne with t-RNA(phe) was investigated using various biophysical techniques. Results of absorption and fluorescence studies revealed that the alkaloid binds to t-RNA exhibiting positive cooperativity. Isothermal titration calorimetry results suggested that the binding of the alkaloid was predominantly enthalpy driven with a smaller favourable entropy term. A surprisingly large favourable component for non-electrostatic contribution to the binding of coralyne to t-RNA was revealed from salt dependence data and the dissection of the free energy. The alkaloid enhanced the thermal stability of t-RNA and the binding affinity values obtained from optical thermal melting data was in agreement with that from calorimetry. The heat capacity change of - 125 cal mol(-1) K-1 and the observed significant enthalpy - entropy compensation phenomenon confirmed the involvement of multiple weak noncovalent interactions. Circular dichroism studies provided evidence for significant perturbation of the t-RNA structure with concomitant induction of optical activity in the bound achiral alkaloid molecules. Binding isotherms generated from circular dichroic data confirmed the cooperative binding mode of the alkaloid as deduced from spectroscopic data. Docking studies provided further insights into the partially intercalated state of coralyne inside the t-RNA structure. This study presents a complete binding and thermodynamic pro. le of coralyne interaction to t-RNA.