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

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.

Keywords:

• Mycobacterium tuberculosis
• tuberculosis
• GTP
• Era
• 16s rRNA
• ribosome
• A. aeolicus

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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Yes, all authors have given their consent.

Disclosure statement

The authors declare no conflict of interest.

Ethical approval

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.

Additional information

Funding

This work was supported by 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).