184 Small molecule identification against novel MDRA protein of Mycobacterium tuberculosis |
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| Authors: | M Kiran Kumar M Vasavi C Venkataramana Reddy |
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| Institution: | 1. Department of Chemistry, Molecular Modelling Research Laboratory , Nizam College, Osmania University , Basheerbagh , 500 001 , Hyderabad;2. Department of Chemistry , JNTUH-CEH, Jawaharlal Nehru Technology University , Kukatpally , 500 085 , Hyderabad |
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| Abstract: | Mycobacterium tuberculosis (Mtb) is an obstinate pathogen causing tuberculosis (TB) in Homo sapiens. One third of the World population is affected by Mtb (James et al., 2008). The multidrug-resistant protein-A (MDRA) belongs to ABC transporter family. The protein MDRA and the membrane integral protein MDRB together form the efflux pump (MDRA2B2 complex) that confers resistance by transport of the drugs out of the cell. The MDRB protein expression depends on the expression of MDRA (Baisakhee et al., 2002). In the present study, MDRA 3-D model (Figure) was generated with the help of comparative homology modeling techniques using pair-wise sequence alignment. The predicted 3-D model was subjected to refinement and validated. The active site of the protein was predicted. The virtual screening (VS) studies were performed at MDRB binding site with an in-house library of small molecules to identify a lead molecule that can inhibits the MDRA protein. The results of VS project competitive inhibitors of MDRB, for its binding with MDRA, and its drug-resistant activity. Hence, the MDRA protein may be treated as a novel target for the development of new chemical entities for tuberculosis therapy (Bhargavi et al., 2010; Malkhed et al., 2011). | |
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