Department of Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Department of Biochemistry, North Eastern Hill University, Shillong, India.
J Biomol Struct Dyn. 2020 Mar;38(4):1083-1093. doi: 10.1080/07391102.2019.1595150. Epub 2019 Apr 7.
Protein-protein interactions are crucial for all biological processes. Compiling this network provides many new insights into protein function and gives directions for the development of new drugs targeted to the pathogen. Nucleoside diphosphate kinase (Mtb Ndk) has been reported to promote survival of mycobacterium within the macrophage and contribute significantly to mycobacterium virulence. Hence, the present study was aimed to identify and characterize the interacting partner for Ndk. The experiments, pull down and far western blotting have demonstrated that Mtb Ndk interacts with Rv1273c, a probable drug ABC transporter ATP-binding protein annotated to export drugs across the membrane. This observation was further confirmed by molecular docking and dynamic simulations studies. The homology model of Rv1273c was constructed and docked with Mtb Ndk for protein-protein interaction analysis. The critical residues involved at interface of Rv1273c-Ndk interaction were identified. MDS and Principal Component analysis carried out for conformational feasibility and stability concluded that the complex between the two proteins is more stable as compared to apo proteins. Our findings would be expected to improve the dissection of protein-protein interaction network and significantly advance our understanding of tuberculosis infection.Communicated by Ramaswamy H. Sarma.
蛋白质-蛋白质相互作用对于所有的生物过程都是至关重要的。编译这个网络提供了许多关于蛋白质功能的新见解，并为开发针对病原体的新药指明了方向。核苷酸二磷酸激酶（Mtb Ndk）已被报道可促进巨噬细胞内分枝杆菌的存活，并对分枝杆菌的毒力有显著贡献。因此，本研究旨在鉴定和表征 Ndk 的相互作用伙伴。下拉和远 Western 印迹实验表明，Mtb Ndk 与 Rv1273c 相互作用，Rv1273c 是一种可能的药物 ABC 转运体 ATP 结合蛋白，注释为将药物跨膜输出。分子对接和动态模拟研究进一步证实了这一观察结果。构建了 Rv1273c 的同源模型，并与 Mtb Ndk 对接进行蛋白质-蛋白质相互作用分析。确定了 Rv1273c-Ndk 相互作用界面上涉及的关键残基。构象可行性和稳定性的 MDS 和主成分分析得出结论，与apo 蛋白相比，两种蛋白质之间的复合物更稳定。我们的发现有望改善蛋白质-蛋白质相互作用网络的剖析，并显著提高我们对结核病感染的理解。通讯作者为 Ramaswamy H. Sarma。
