Modeling the Interactions of Herbal Drugs to β-ketoacyl ACP Synthase ofMycobacterium tuberculosisH37Rv

Abstract

The present paper reports a bio-computational study carried out with the aim of understanding the binding mode of anti-TB herbal ligands onto the homology modeled structure of fatty acid synthase of Mycobacterium tuberculosis (M.tb) H37Rv. Sequence alignment of beta-ketoacyl ACP synthase (KAS) domain of the protein with other related KAS sequences of PDB database revealed high degree of sequence variation. However, the catalytic triad comprising of CHH (cys150-his279-his320) was found to be conserved in the KAS sequence of M.tb H37Rv. The tertiary structure of this protein predicted using genetic algorithm operator in the MODELLER package appeared to give a satisfactory structure for the purpose of studying ligand and substrate binding pockets on the protein. PDB templates complexed with ligands (citric acid and lauric acid) were used for model building. Docking studies carried out with different herbal ligands suggest that, aloe-emodin and nimbin are the best herbal candidates to replace the synthetic drugs 'thiolactomycin/cerulenin'.

Host−Guest System of Nimbin and β-Cyclodextrin or Its Derivatives: Preparation, Characterization, Inclusion Mode, and Solubilization

“…For example, nimbin has been shown to be 4 times as effective as the steroid hydrocortisone in the treatment of eczema and psoriasis, but without side effects such as thinning of the skin . Additionally, docking studies carried out with different herbal ligands suggest that nimbin is one of the best herbal candidates to replace the synthetic drugs thiolactomycin and cerulenin . However, the use of nimbin and other limonoids as biopesticides or herbal medicines is greatly limited by its low water solubility and bioavailability , .…”