Indian Journal of Bioinformatics and Biotechnology

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Interactome Analysis of Devs Protein Involved in Persistence of Mycobacterium tuberculosis and Design of Inhibitor against its Interacting Persister Protein: an Approach to Inhibit Protein-protein Interaction


Affiliations
1 Department of Biotechnology and Bioinformatics, North Eastern Hill University, Shillong-793022, India
2 Centre for Advanced studies in Crystallography and Biophysics, University of Madras, Guindy (Maraimalai) Campus, Chennai- 600 025, India
 

Background: Mycobacterium tuberculosis has been a potential threat for humans for ages. Its invulnerability to various drugs and persistency has emerged as a stumbling block in eradicating the pathogenecity of the bacteria. A protein-protein interaction network of redox sensor histidine kinase response regulator (devS), a member of the two- component regulatory system devR/devS is known to be involved in onset of the dormancy response acting as a redox sensor was studied. Methods: An interactome level analysis of devS with other proteins involved is essential to gain insights into the proteins involvement in persistence of tuberculosis. Folding pattern of the proteins involved in the interaction was analyzed and molecular docking was performed to understand the protein-ligand interaction. Result: DevS protein directly interacts with high confidence with transcriptional regulatory protein (devR) protein forming a two-component system, probable transcriptional regulatory (narL) protein and a universal stress protein (MT3220). Hypoxia sensor histidine kinase response regulator dosT (MT2086) interact with the two-component regulatory system devR/devS involved in dormancy and is structurally aligned with devS protein. The folding patterns of devS, MT2086 and MT0867 are similar but at a different folding rate. Conslusion: DevS is shown to interact with devR protein with high confidence, which is involved in the two-component system. A better interaction is seen with piperine, berberine and allin with all the four target proteins.

Keywords

Mycobacterium tuberculosis, Persister Proteins, Interactome
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  • Interactome Analysis of Devs Protein Involved in Persistence of Mycobacterium tuberculosis and Design of Inhibitor against its Interacting Persister Protein: an Approach to Inhibit Protein-protein Interaction

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Authors

Sandeep Tiwari
Department of Biotechnology and Bioinformatics, North Eastern Hill University, Shillong-793022, India
Baphilinia Jones Mylliemngap
Department of Biotechnology and Bioinformatics, North Eastern Hill University, Shillong-793022, India
Devadasan Velmurugan
Centre for Advanced studies in Crystallography and Biophysics, University of Madras, Guindy (Maraimalai) Campus, Chennai- 600 025, India
Atanu Bhattacharjee
Department of Biotechnology and Bioinformatics, North Eastern Hill University, Shillong-793022, India

Abstract


Background: Mycobacterium tuberculosis has been a potential threat for humans for ages. Its invulnerability to various drugs and persistency has emerged as a stumbling block in eradicating the pathogenecity of the bacteria. A protein-protein interaction network of redox sensor histidine kinase response regulator (devS), a member of the two- component regulatory system devR/devS is known to be involved in onset of the dormancy response acting as a redox sensor was studied. Methods: An interactome level analysis of devS with other proteins involved is essential to gain insights into the proteins involvement in persistence of tuberculosis. Folding pattern of the proteins involved in the interaction was analyzed and molecular docking was performed to understand the protein-ligand interaction. Result: DevS protein directly interacts with high confidence with transcriptional regulatory protein (devR) protein forming a two-component system, probable transcriptional regulatory (narL) protein and a universal stress protein (MT3220). Hypoxia sensor histidine kinase response regulator dosT (MT2086) interact with the two-component regulatory system devR/devS involved in dormancy and is structurally aligned with devS protein. The folding patterns of devS, MT2086 and MT0867 are similar but at a different folding rate. Conslusion: DevS is shown to interact with devR protein with high confidence, which is involved in the two-component system. A better interaction is seen with piperine, berberine and allin with all the four target proteins.

Keywords


Mycobacterium tuberculosis, Persister Proteins, Interactome

References