Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0045947
Title: Validation of Drug-Like Inhibitors against Mycobacterium Tuberculosis L-Aspartate α-Decarboxylase Using Nuclear Magnetic Resonance (1H NMR)
Authors: Sharma, R.
Florea, M.
Nau, W.M.
Swaminathan, K. 
Issue Date: 28-Sep-2012
Citation: Sharma, R., Florea, M., Nau, W.M., Swaminathan, K. (2012-09-28). Validation of Drug-Like Inhibitors against Mycobacterium Tuberculosis L-Aspartate α-Decarboxylase Using Nuclear Magnetic Resonance (1H NMR). PLoS ONE 7 (9) : -. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0045947
Abstract: The catalytic activity of L-aspartate α-decarboxylase (ADC) is essential for the growth of several micro-organisms, including Mycobacterium tuberculosis (Mtb), and has triggered efforts for the development of pharmaceutically active compounds against tuberculosis. The present study is a continuation of our recent chemoinformatics-based design approach for identifying potential drug-like inhibitors against MtbADC. We report an NMR-based protocol that allows label-free and direct monitoring of enzymatic conversion, which we have combined with a systematic testing of reported and newly identified potential inhibitors against MtbADC. Quantification of enzymatic conversion in the absence and presence of inhibitors allowed for a relative measure of the inhibitory effect (krel). Among the newly identified compounds, D-tartrate, L-tartrate, and 2,4-dihydroxypyrimidine-5-carboxylate were found to inhibit the enzyme with krel values of 0.36, 0.38, and 0.54, respectively. In addition to the identification of potential building blocks for the development of therapeutic agents, the current study highlights the importance of electrostatic interactions governing enzyme-inhibitor binding. © 2012 Sharma et al.
Source Title: PLoS ONE
URI: http://scholarbank.nus.edu.sg/handle/10635/102136
ISSN: 19326203
DOI: 10.1371/journal.pone.0045947
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
2012-validation_drug-like_inhibitors_against_mycobacterium-pub.pdf456.79 kBAdobe PDF

OPEN

PublishedView/Download

SCOPUSTM   
Citations

2
checked on Dec 18, 2018

WEB OF SCIENCETM
Citations

2
checked on Dec 18, 2018

Page view(s)

48
checked on Dec 14, 2018

Download(s)

2
checked on Dec 14, 2018

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.