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Molecular Docking Studies of Mycobacterium tuberculosis RNA Polymerase β Subunit (rpoB) Receptor

Authors: Virupakshaiah DBM, Madiha Ahmed, Smita T. Patil, Chandrakanth Kelmani


Tuberculosis (TB) is a bacterial infectious disease caused by the obligate human pathogen, Mycobacterium tuberculosis. Multidrug-resistant tuberculosis (MDR-TB) is a global reality that threatens tuberculosis control. Resistance to antibiotic Rifampicin, occurs in 95% of cases through nucleotide substitutions in an 81-bp core region of the rpoB i.e; beta subunit of DNA dependant RNA polymerase. In this paper, we studied the Rifampicin-rpoB receptor interactions In silico. First, homology modeling was performed to obtain the three dimensional structure of Mycobacterium rpoB. Sixty analogs of Rifampicin were prepared using Marvin sketch software. Both original Rifampicin and the analogs were docked with rpoB and energy values were obtained. Out of sixty analogs, 43 analogs had lesser energy values than conventional Rifampicin and hence are predicted to have greater binding affinity to rpoB. Thus, this study offers a route for the development of Rifampicin analogs against multi drug resistant Mycobacterium rpoB.

Keywords: Mycobacterium Tuberculosis, rifampicin, rpoB, Marvin Sketch

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[1] R. Johnson, E.M. Streicher, G.E. Louw, R.M. Warren, P.D. Helden and T.C.Victor, "Drug Resistance in Mycobacterium tuberculosis" in Curr. Issues Mol. Biol.2006, 8: pp 97-112.
[2] M. Lipsitch and B.R. Levin, " Population dynamics of tuberculosis treatment: mathematical models of the roles of non-compliance and bacterial heterogeneity in the evolution of drug resistance, in Int. J. Tuberc. Lung Dis. 1998, 2:pp 187-199.
[3] C.N. Paramasivan and P. Venkataraman, "Drug resistance in tuberculosis in India", Review Article in Indian J. Med. Res. 2004, 120: pp377-386.
[4] F.A. Drobniewski and S.M. Wilson, "The rapid diagnosis of isoniazid and rifampin resistance in Mycobacterium tuberculosis: a molecular story" in J.Med. Microbiol. 1998 47:pp189-196.
[5] A. Somoskovi, L.M. Parsons and M. Salfinger, "The molecular basis of resistance to isoniazid, rifampin, and pyrazinamide in Mycobacterium tuberculosis", Review Article in Respiratory Research 2001, 2 (3) :pp 164-168.
[6] W. Wehrli, "Rifampin:Mechanisms Of Action And Resistance", in Clin Infect.Dis.1983, 5(3): pp S407-S411.
[7] S. Ramaswamy and J.M. Musser, " Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update", in Tuberc. Lung Dis. 1998, 79:pp 3-29.
[8] E.A. Campbell , N. Korzheva ., A. Mustaev, K. Murakami , S. Nair, A. Goldfarb and S.A. Darst S.A., " Structural Mechanism for Rifampicin nhibition of Bacterial RNA polymerase", in Cell 2001, 104:pp 901-912.
[9] S.T. Cole, R. Brosch, J. Parkhill, T. Garnier, C. Churcher, D. Harris , S.V. Gordon, K. Eiglmeier, S. Gas and C.E. Barry, " Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence," in Nature 1998, 393: pp 537-544.
[10] L. Kant, "Translational Research In Tuberculosis: Bridging The Long Journey From Bench To Bedside", in The Indian Journal Of Tuberculosis 2005, 52:pp117- 119.
[11] H.M. Berman , J. Westbrook, Z. Feng, G. Gilliland, T.N. Bhat, H. Weissig, I.N. Shindyalov and P.E. Bourne, "The Protein Data Bank", in Nucleic Acids Research, 2000, 28: pp 235-242.
[12] S.F Altschul , W.Gish , W. Miller, E.W. Myers and D.J. Lipman , "Basic local alignment search tool", in J. Mol. Biol. 1990,215:pp 403- 410.
[13] S.F. Altschul, T.L Madden, A.A. Schaffer, J. Zhang, Z. Zhang, W.Miller and D.J. Lipman, "Gapped BLAST and PSI-BLAST: a new generation of protein database search programs", in Nucleic Acids Res. 1997, 50: pp3389-3402.
[14] D.J. Lipman, S.F. Altschul and J.D. Kececioglu, " A tool for multiple sequence alignment", in Proc Natl Acad Sci U S A, 1989, 86(12):pp 4412-4415.
[15] R. Chenna, H. Sugawara , T. Koike, R. Lopez , T.J. Gibson , D.G. Higgins J.D.Thompson, "Multiple sequence alignment with the Clustal series of programs", in Nucleic Acids Res. 2003, 31 (13): pp3497- 3500.
[16] F. Sievers, A. Wilm , D.G. Dineen , T.J. Gibson, K. Karplus, W.Li, R.Lopez, H. McWilliam, M. Remmert, J. Söding , J.D. Thompson and D.G.Higgins, "Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega", in Mol Syst Biol 2011, pp77:539.
[17] S.B. Needleman and C.D. Wunsch, "A general method applicable to the search for similarities in the amino acid sequence of two proteins", Journal of Molecular Biology, 1970, 48 (3): pp443-53.
[18] N.Guex and M.C. Peitsch, "SWISS-MODEL and the Swiss- PdbViewer:an environment for comparative protein modeling.", in Electrophoresis, 1997, 18: pp2714-2723.
[19] C.O.Pardo , A. Cordero, J.R. Martinez and S. Imperial, "Homology modeling of M. tuberculosis 2C-methyl-D-erythritol-4- phosphate cytidylyltransferase, the third enzyme of the MEP pathway for isoprenoid biosynthesis, Journal of Molecular Modelling,2009, pp 1-45.
[20] R.A.Laskoswki , M.W. MacArthur , D.S. Moss and J.M.Thornton, "PROCHECK: a program to check the stereo chemical quality of protein structures", J. Appl. Cryst.,1993, 26:pp283-291.
[21] S.P. Nataraj , P.B. KaviKishor, V.C.K. Reddy, P.E. Kumar, A.Anitha, R.M.Kumar and R.L.Ananda, "Comparative Modeling and Docking Studies of Mycobacterium tuberculosis H37RV rpoB Protein", in Internet Electronic Journal of Molecular Design, 2008, 7: pp12-29.
[22] M.A.Bauer, S. Lu , J.B. Anderson, F. Chitsaz , M.K. Derbyshire, C. De Wesse-Scott, J.H. Fong , L.Y. Geer , R.C. Geer , N.R. Gonzales , M. Gwadz , D.I. Hurwitz , J.D. Jackson, Z. Ke , C.J. Lanczycki, F. Lu, G.H. Marchler, M. Mullokandov, M.V. Omelchenko, C.L. Robertson, J.S. Song., N. Thanki., R.A. Yamashita, D.Zhang., N. Zhang ., C.Zheng., S.H. Bryant , "CDD: a Conserved Domain Database for the functional annotation of proteins. Nucleic Acids Research, 2011, 39:pp 225-229.
[23] A User Guide for Marvin Sketch from
[24] D.W.Ritchie and G.J.L.Keg, "Protein Docking Using Spherical Polar Fourier Correlations",in Proteins:Struct.Funct.Genet., 2000,39:pp94- 178.
[25] D.W.Ritchie, "Hex 6.3 User Manual Protein Docking Using Spherical Polar Fourier Correlations", Copyright 1996-2010.
[26] U,H. Patel, R.A.Barot, B.D.Patel , D.A.Shah and R.D. Modh," Docking studies of pyrrole derivatives using Hex", in International Journal of Environmental Sciences, 2012, 2(3):pp 1765-1770.
[27] K.S. Murakami , S. Masuda and S.A. Darst, "Structural basis of transcription initiation:RNA polymerase holoenzyme at 4 A0 resolution" , in Science,2002, 296(5571):pp 1280-4.
[28] C.I├▒aki, J. Chakravartti, P.M. Small, J. S. Galagan, K.Kremer, J.D.Ernst and S.Gagneux, "Human T cell epitopes of Mycobacterium tuberculosisare evolutionarily hyperconserved", in Nature Genetics,2010. 42:498- 503.
[29] S.B.Silverman, "The Organic Chemistry of Drug Design and Drug Action,Chapter 2: Drug Discovery, Design And Development, Section 2.2: Lead Modification", Edition 2,2004 :pp 18-34.