A study of communication pathways in methionyl-tRNA synthetase by molecular dynamics simulations and structure network analysis
A study of communication pathways in methionyl-tRNA synthetase by molecular dynamics simulations and structure network analysis
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DOI：
10.1073/pnas.0704459104
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发表时间：
2007-10-02
影响因子：
11.1
通讯作者：
Vishveshwara, Saraswathi
中科院分区：
文献类型：
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作者：
Ghosh, Amit;Vishveshwara, Saraswathi
tRNA合成酶家族的酶通过同步识别在空间上相隔约70埃的抗结肠区和氨基酰化区来高精度地发挥其功能。这种精确的功能是通过在两个区域之间建立良好的通信路径来实现的。我们模拟了由大肠杆菌甲硫基-tRNA合成酶（mems）、tRNA和活化的蛋氨酸组成的复合物的结构。对模型结构进行了分子动力学模拟，得到了配合物的平衡结构，并对其残基间的相互关系进行了评价。此外，对这些模拟结构进行了网络分析，以阐明激活位点和抗结肠识别位点之间的通信路径。本研究提供了详细的传播路径，与实验结果一致。在无配体天然酶的配合物（MetRS +活化蛋氨酸）和（MetRS + tRNA）上也进行了类似的研究。通过对四种模拟得到的路径进行比较，可以清楚地表明，通信路径与tRNA和活化的蛋氨酸结合的酶复合物具有很强的相关性和独特性。本文详细介绍了我们的研究方法和结果的生物学意义。这里开发的方法也可以用于研究任何通过远距离通信发生功能的蛋白质系统。
The enzymes of the family of tRNA synthetases perform their functions with high precision by synchronously recognizing the anticoclon region and the aminoacylation region, which are separated by approximate to 70 angstrom in space. This precision in function is brought about by establishing good communication paths between the two regions. We have modeled the structure of the complex consisting of Escherichia coli methionyl-tRNA synthetase (MetRS), tRNA, and the activated methionine. Molecular dynamics simulations have been performed on the modeled structure to obtain the equilibrated structure of the complex and the cross-correlations between the residues in MetRS have been evaluated. Furthermore, the network analysis on these simulated structures has been carried out to elucidate the paths of communication between the activation site and the anticoclon recognition site. This study has provided the detailed paths of communication, which are consistent with experimental results. Similar studies also have been carried out on the complexes (MetRS + activated methonine) and (MetRS + tRNA) along with ligand-free native enzyme. A comparison of the paths derived from the four simulations clearly has shown that the communication path is strongly correlated and unique to the enzyme complex, which is bound to both the tRNA and the activated methionine. The details of the method of our investigation and the biological implications of the results are presented in this article. The method developed here also could be used to investigate any protein system where the function takes place through long-distance communication.