Abstract
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.
Communicated by Ramaswamy H. Sarma
HIGHLIGHTS
MtEra protein carries five GTP binding motifs (G1, G2, G3, G4 and G5) and one KH domain for RNA binding.
Multifunctional role of MtEra predicted in processes like catabolic, metabolic and ribosome biogenesis.
Point mutation analysis showed the importance of tryptophan (W) and lysine (K) residues at position 288 and 19 in stability and activity of the protein, respectively.
Dynasore inhibitor showed the highest binding energy of −9 kcal/mol for MtEra.
Acknowledgments
The authors acknowledge financial support from the Department of Science and Technology – SERB, Council of Scientific and Industrial Research-Institute of Genomics and Integrative Biology under the research project GAP0145 (SERB-DST Grant no: EEQ/2016/000514).
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The authors declare no conflict of interest.
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This article does not contain any studies with human participants or animals performed by any of the authors.
Author contributions
PA conceptually analyzed the work, wrote the manuscript, designed and generated all the figures; AK helped in assisting the manuscript correctness, did the inhibitors and MD simulation work and LSM helped in writing, correctness and also handled all the corresponding activities.
Data availability statement
Yes, the authors agreed that the availability of data ensures data transparency norms.