Decoding the structural integrity and multifunctional role of Era protein in the survival of Mycobacterium tuberculosis H37Rv.

Era, a widely known GTP binding protein found in many organisms including prokaryotes and eukaryotes and plays a significant role in many fundamental cellular processes like cell growth, differentiation and signaling. In Mycobacterium tuberculosis (Mtb) H₃₇Rv, Era protein had been proved as a GTPase protein but its structural and functional insights are still lacking. Through comparative analysis, structural modeling, docking and using various bioinformatic tools, a detailed investigation of Era was carried out to deduce the structure, function and residues involved in the activity of the protein. Intriguingly, docking results revealed high binding affinity of Era not only with GTP but also with ATP. Myristoylation modifications and phosphorylations on Era were predicted to possibly aid in regulating Era activity and localization; and also the role of Era in translation regulation was foreseen by showing its association with 16s rRNA. Moreover, point mutation of Era residues revealed the effect of W288G and K19G in highly destabilizing the protein structure and activity. Additionally, Era protein was docked with 25 GTPase/ATPase inhibitors, where, Dynasore inhibitor showed the highest affinity for the protein's GTP binding sites and can be used for further drug trials to inhibit growth of mycobacteria.