Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0033521
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dc.titleChemoinformatic identification of novel inhibitors against Mycobacterium tuberculosis l-aspartate α-decarboxylase
dc.contributor.authorSharma, R.
dc.contributor.authorKothapalli, R.
dc.contributor.authorvan Dongen, A.M.J.
dc.contributor.authorSwaminathan, K.
dc.date.accessioned2014-05-19T02:50:35Z
dc.date.available2014-05-19T02:50:35Z
dc.date.issued2012-03-28
dc.identifier.citationSharma, R., Kothapalli, R., van Dongen, A.M.J., Swaminathan, K. (2012-03-28). Chemoinformatic identification of novel inhibitors against Mycobacterium tuberculosis l-aspartate α-decarboxylase. PLoS ONE 7 (3) : -. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0033521
dc.identifier.issn19326203
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/52826
dc.description.abstractL-Aspartate α-decarboxylase (ADC) belongs to a class of pyruvoyl dependent enzymes and catalyzes the conversion of aspartate to β-alanine in the pantothenate pathway, which is critical for the growth of several micro-organisms, including Mycobacterium tuberculosis (Mtb). Its presence only in micro-organisms, fungi and plants and its absence in animals, particularly human, make it a promising drug target. We have followed a chemoinformatics-based approach to identify potential drug-like inhibitors against Mycobacterium tuberculosis L-aspartate α-decarboxylase (MtbADC). The structure-based high throughput virtual screening (HTVS) mode of the Glide program was used to screen 333,761 molecules of the Maybridge, National Cancer Institute (NCI) and Food and Drug Administration (FDA) approved drugs databases. Ligands were rejected if they cross-reacted with S-adenosylmethionine (SAM) decarboxylase, a human pyruvoyl dependent enzyme. The lead molecules were further analyzed for physicochemical and pharmacokinetic parameters, based on Lipinski's rule of five, and ADMET (absorption, distribution, metabolism, excretion and toxicity) properties. This analysis resulted in eight small potential drug-like inhibitors that are in agreement with the binding poses of the crystallographic ADC:fumarate and ADC:isoasparagine complex structures and whose backbone scaffolds seem to be suitable for further experimental studies in therapeutic development against tuberculosis. © 2012 Sharma et al.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1371/journal.pone.0033521
dc.sourceScopus
dc.typeArticle
dc.contributor.departmentBIOLOGICAL SCIENCES
dc.contributor.departmentDUKE-NUS GRADUATE MEDICAL SCHOOL S'PORE
dc.description.doi10.1371/journal.pone.0033521
dc.description.sourcetitlePLoS ONE
dc.description.volume7
dc.description.issue3
dc.description.page-
dc.identifier.isiut000304489000021
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