Book of Abstracts: Albany 2007

category image Albany 2007
Conversation 15
June 19-23 2007

Docking of Anti-TB Herbal Ligands Onto Homology Modeled Fatty Acid Synthase Protein (NP_217040) of Mycobacterium tuberculosis H37Rv

A bio-computational study was carried out with the aim of understanding the binding mode of anti-TB herbal ligands onto the homology modeled structure of fatty acid synthase (FAS) of Mycobacterium tuberculosis H37Rv. Submission of the whole sequence of FAS (3,069 amino acids) to MODWEB, a web based server for automated comparative protein structure modeling (1), resulted in generating 14 tertiary structures, with the sequence identity between the target and the template in the range of 10 to 28%. Model score was observed to be more than 0.6 for eight of these structures. Based on SCANPROSITE (2) results, it was possible to conclude that, among these eight structures, FAS protein with sequence boundary of 2579-2992 amino acid residues (sequence identity: 21%; model score: 1.00), appeared to have β-keto acyl synthase activity, with cysteine as the active site residue. Since this site is considered to be a potential drug target, loop modeled structure of this protein was considered for docking studies. Docking of four herbal ligands with anti-TB activity [allocuspareine (3); β-amyrin (4); nimbin (5); ursolic acid (6)] using AUTODOCK (7) revealed that, all these ligands got docked with much lower energy than isoniazid, the drug to which the mycobacterium is resistant. The results of these studies suggest alternative therapy to cure TB using herbal medicines, which has much lesser side effects than the synthetic drugs.

References and Footnotes
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  2. Gattiker, A., Gasteiger, E., and Bairoch, A. Appl. Bioinformatics 1, 107?108 (2002).
  3. Houghton, P. J., Woldemariam, T. Z., Watanabe, Y., and Yates M. Planta Med. 65, 250-254 (1999).
  4. Sanches, N. R., Cortez, D. A. G., Schiavini, M. S., Nakamura, C. V., and Filho, B. P. D. Brazilian Archives of Biology and Technology 48, 429-436 (2005).
  5. Siddiqui, S., Faizi, S., Siddiqui, B. S., and Ghiasuddin. J. Nat. Prod. 55, 303-310 (1992).
  6. Jimenez, A., Meckes, M., Alvarez, V., Torres, J., and Parra, R. Phytother. Res. 19, 320-322 (2005).
  7. Morris, G. M., Goodsell, D. S., Hallidey, R., Huey, R., Hart, W. E., Blew, R. K., and Olson, A. J. J.Computational Chemistry 19, 1639-1662 (1998).

Ramesh K V
Kaushiki Wagle
Sudha Deshmukh*

Center for Postgraduate Studies
Sri Bhagawan Mahaveer Jain College
18/3, 9th Main
Jayanagar 3rd Block
Bangalore 560011, India

*Phone: +91(080) 41210694
Fax: +91(080) 41210692
Email: sudhadeshmukh@yahoo.com