Book of Abstracts: Albany 2007
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
Ramesh K V
Center for Postgraduate Studies