Kannappan Prabhavathy, Narayanan Sundarabaalaji
Structural Biology Lab, Department of Bioinformatics, School of Life Sciences, Bharathiar University, Coimbatore - 641046, India.
Bioinformation. 2011;6(8):303-6. doi: 10.6026/97320630006303. Epub 2011 Jul 6.
Yellow fever virus is the causative agent of Yellow fever. The genome of the virus contains three structural and seven non-structural proteins. Of these seven nonstructural proteins, NS2B-NS3 protein complex has protease activity required for viral replication. Predicting the 3D structure of this complex and studying the interaction of residues at the recognized catalytic triad of the complex is an integral part to understand the virus replication mechanism. In the present study, the structure was determined for NS2B-NS3 complex by Homology modeling and modeled structure was validated for its stability. Mutation studies at the residues His94, Asp118 and Ser176 revealed that Asp118-His94 bond played an important role in the structural stability of NS2B-NS3 complex. This indicates site-directed mutagenesis, controlling YFV replication, as one mechanism to design vaccine strains. Docking studies of the bioactive compounds at the active site of NS2B-NS3 complex also indicated 4-hydroxypanduratin A as potential lead compound for drug development. The theoretical models will further pave way to experimentally verify our mutation and docking studies, thus taking a lead in pharmacogenomics and drug development.
YFV - Yellow Fever Virus, WNV - West Nile Virus, H-bonds - hydrogen bonds, SNP - Single nucleotide polymorphism.
黄热病病毒是黄热病的病原体。该病毒的基因组包含三种结构蛋白和七种非结构蛋白。在这七种非结构蛋白中，NS2B-NS3蛋白复合物具有病毒复制所需的蛋白酶活性。预测该复合物的三维结构并研究其公认催化三联体中残基的相互作用是理解病毒复制机制的重要组成部分。在本研究中，通过同源建模确定了NS2B-NS3复合物的结构，并对建模结构的稳定性进行了验证。对His94、Asp118和Ser176残基的突变研究表明，Asp118-His94键在NS2B-NS3复合物的结构稳定性中起重要作用。这表明定点诱变作为控制黄热病病毒复制的一种机制，可用于设计疫苗株。对生物活性化合物在NS2B-NS3复合物活性位点的对接研究还表明，4-羟基潘杜拉亭A是药物开发的潜在先导化合物。这些理论模型将进一步为通过实验验证我们的突变和对接研究铺平道路，从而在药物基因组学和药物开发方面领先一步。
YFV - 黄热病病毒，WNV - 西尼罗河病毒，H键 - 氢键，SNP - 单核苷酸多态性
