A novel transacetylase (TAase) function of glutamine synthetase (GS) in bacterial species such as Mycobacterium smegmatis and Mycobacterium tuberculosis H37Rv 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 of M. tuberculosis GS. PAs were predicted to bind M. tuberculosis GS on the protein surface away from the known active site of GS. Subsequent focussed/refined docking of potent PA with GS showed that the ε-amino group of Lys4 of GS formed a cation-π interaction 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.
Introduction: WhatsApp is one of the most popular tool of mass media communication besides Facebook and twitter. We all agree a good communication is essential between the teacher and student for a healthy academic environment in every discipline and it is must in Anatomy because of immenseness of this basic science as well as its exposure to the students in a short span. To ease this burden and to facilitate the teaching learning outcome we incorporated WhatsApp shared learning as an adjuvant to class-room teaching. So we created a group dedicated to anatomical discussion for MBBS 2015-16 batch. We discussed the current curricular topics, relevant queries and provided the students the multimedia resource as and when needed. The outcome of this was analysed and discussed through peer reviewed questionnaire and suggestions.
The present study clearly demonstrated the in vitro antitubercular potential of the novel drug candidate NA5. Further studies are warranted to establish the in vivo efficacy and therapeutic potential of NA5.
The protein acetyltransferase (MTAase) function of glutamine synthetase of Mycobacterium smegmatis was established earlier. In this paper, studies were undertaken to examine MTAase function of recombinant glutamine synthetase (rGlnA1) of Mycobacterium tuberculosis, which showed >80% similarity with M. smegmatis GlnA. The specificity of MTAase to several acyl derivative of coumarins was examined. The results clearly indicated that MTAase exhibited differential specificities to several acyloxycoumarins. Further, MTAase was also found capable of transferring propionyl and butyryl groups from propoxy and butoxy derivatives of 4-methylcoumarin. These observations characterized MTAase in general as a protein acyltransferase. MTAase catalyzed acetylation of GST by 7,8-diacetoxy-4-methylcoumarin (DAMC), a model acetoxy coumarin was confirmed by MALDI-TOF-MS as well as western blot analysis using acetylated lysine polyclonal antibody. In order to validate the active site of rGlnA1 for TAase activity, effect of DAMC and L-methionine-S-sulfoximine (MSO) on GS and TAase activity of rGlnA1 were studied. The results indicated that the active sites of GS and TAase were found different. Acetyl CoA, a universal biological acetyl group donor, was also found to be a substrate for MTAase. These results appropriately characterize glutamine synthetase of Mtb exhibiting transacylase action as a moonlighting protein.
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