Affiliation:
1. Faculty of Applied Sciences Ton Duc Thang University Ho Chi Minh City Vietnam
2. Faculty of Chemical Engineering Ho Chi Minh City University of Technology Ho Chi Minh City Vietnam
3. Department of Biomedical Sciences and Engineering National Central University Taoyuan Taiwan
Abstract
Abstract
Tuberculosis (TB) is one of the most dangerous infectious diseases and is caused by Mycobacterium bovis (Mb) and Mycobacterium tuberculosis (Mt). Branched-chain amino acid aminotransferases (BCATs) were reported to be the key enzyme for methionine synthesis in Mycobacterium. Blocking the methionine synthesis in Mycobacterium can inhibit the growth of Mycobacterium. Therefore, in silico screening of inhibitors can be a good way to develop a potential drug for treating TB. A pyridoxal 5′-phosphate (PLP)-form of Mycobacterium bovis branched-chain amino acid aminotransferases (MbBCAT), an active form of MbBCAT, was constructed manually for docking approximately 150 000 compounds and the free energy was calculated in Autodock Vina. The 10 compounds which had the highest affinity to MbBCAT were further evaluated for their inhibitory effects against MbBCAT. Within the selected compounds, compound 4 (ZINC12359007) was found to be the best inhibitor against MbBCAT with the inhibitory constant Ki of 0·45 μmol l−1 and IC50 of 2·37 μmol l−1. Our work provides potential candidates to develop effective drugs to prevent TB since the well-known structural information would be beneficial in the structure-based modification and design.
Publisher
Oxford University Press (OUP)
Subject
Applied Microbiology and Biotechnology
Cited by
3 articles.
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