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Title |
Designing novel inhibitors against Mycobacterium tuberculosis FadA5 (acetyl-CoA acetyltransferase) by virtual screening of known anti-tuberculosis (bioactive) compounds
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Authors |
Atul Kumar Jaiswal1, Syed Hussain Abbas Husaini2, Amarjeet Kumar1, Naidu Subbarao1*
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Affiliation |
1School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi, India; 2Department of Bio-Engineering, Integral University, Lucknow, Uttar Pradesh, India;
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Article Type |
Hypothesis
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Date |
Received May 18, 2018; Revised June 10, 2018; Accepted June 11, 2018; Published June 30, 2018
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Abstract |
By-products of fatty acid degradation are extensively utilized by Mycobacterium tuberculosis (Mtb) for lipid synthesis and energy production during infection phase. Cholesterol from host is scavenged by Mtb to fulfill its metabolic requirements, evade host immunity and invade macrophages. Blocking cholesterol catabolic pathways leads to bacteriostasis. FadA5 (Acetyl-CoA acetyltransferase), a thiolase encoded by fadA5 (Rv3546) gene in Mtb, plays crucial role in cholesterol aliphatic chain degradation. Hence, FadA5 is a potential target for designing antitubercular inhibitors. In this study, 60,284 antituberculosis (bioactive) compounds from ChEMBL database and analogous library from ZINC database of commercially available compounds have been screened against FadA5 active site to identify compounds having inhibitory potential against both the apo (state I) and intermediate (state II) states of FadA5. Altogether, this study reports 7 potential inhibitors against two functional states of FadA5, which can be further taken for invitro studies.
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Keywords |
Inhibitors, Mycobacterium tuberculosis, FadA5, virtual screening, molecular docking
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Citation |
Jaiswal et al. Bioinformation 14(6): 327-336 (2018)
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Edited by |
P Kangueane
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ISSN |
0973-2063
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Publisher |
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License |
This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.
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