Dissecting druggability of ABC transporter proteins in Mycobacterium species through network modeling
| Autor: | Ritika Kabra, Bhagwat Lad, Shailza Singh, Prajakta Ingale |
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| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
Siderophore biology In silico 030303 biophysics Druggability ATP-binding cassette transporter Transporter General Medicine Computational biology biology.organism_classification Mycobacterium tuberculosis 03 medical and health sciences Protein structure Structural Biology Molecular Biology Mycobacterium |
| Zdroj: | Journal of Biomolecular Structure and Dynamics. 40:8365-8374 |
| ISSN: | 1538-0254 0739-1102 |
| Popis: | Mycobacterium tuberculosis (Mtb) is an infectious disease that affects nearly 9.6 million people every year. Metals are important determinants of growth and pathogenicity of mycobacterium. In the present study, we have analyzed protein-protein interaction networks belonging to the iron, sulfur and molybdenum metabolism of Mycobacterium. Our analysis has identified some of the important target proteins one among them being irtA. Iron taken up by siderophores from the host is transported to irtA through which iron enters Mycobacterium. Thus, irtA plays a major role as an iron transporter in Mycobacterium. As irtA protein structure was not solved experimentally, we have predicted 3D structure of irtA. After successful model evaluation, we have identified thiosemicarbazones as possible drug candidates for irtA. Henceforth, we have designed five analogues of thiosemicarbazones and tested in silico for their efficacy against irtA using molecular docking, among them analogue 1 showed a very good efficacy.Communicated by Ramaswamy H. Sarma. |
| Databáze: | OpenAIRE |
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