Albany 2013: Book of Abstracts
June 11-15 2013
©Adenine Press (2012)
Small molecule identification against novel MDRA protein of Mycobacterium tuberculosis
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 multi-drug 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 3D model (Figure) was generated with the help of comparative homology modeling techniques using pair wise sequence alignment. The predicted 3D 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 inhibit 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 (NCEs) for tuberculosis therapy (Malkhed et.al., 2010 Bhargavi et.al., 2010).
S. C. Baisakhee, B. Sanjib, B. Rajib, B. Joyoti, K. Manikuntala and C. Parul, (2002), Overexpression and functional characterization of an ABC (ATP-binding cassette) transporter encoded by the genes drrA and drrB of Mycobacterium tuberculosis., Biochem. J. 367: 279-285
M. Kiran Kumar1
1Molecular Modelling Research Laboratory