Abstract
A novel transacetylase (TAase) function of glutamine synthetase (GS) in bacterial species such asMycobacterium smegmatisandMycobacterium tuberculosisH37Rv was established by us, termed as mycobacterial TAase (MTAase). Several polyphenolic acetates (PAs) were found to be substrates for MTAase by inhibiting certain receptor proteins such as glutathione S-transferase by way of acetylation. The present work describes the descriptor-based 2D-QSAR studies developed for a series of PA synthesized by us and evaluated for MTAase and antimycobacterial activity using stepwise multiple linear regression method with the kinetic constants and the minimum inhibitory constant (MIC) as the dependent variables, to address the fact that TAase activity was leading to the antimycobacterial activity. Further, blind docking methods using AutoDock were carried out to study the interaction of potent PA with the crystal structure ofM. tuberculosisGS. PAs were predicted to bindM. tuberculosisGS on the protein surface away from the known active site of GS. Subsequent focussed/refined docking of potent PA with GS showed that theε-amino group of Lys4 of GS formed a cation-πinteraction with the benzene ring of PA. Also, ADMET-related descriptors were calculated to predict the pharmacokinetic properties for the selection of the effective and bioavailable compounds.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
More From: ISRN Structural Biology
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.