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Article

Exploring the Molecular Basis for Binding of Inhibitors by Threonyl-tRNA Synthetase from Brucella abortus: A Virtual Screening Study

by 1,2,†, 1,2,†, 1,2,†, 1,2, 1,2, 1,2, 1,2,3,* and 1,2,3
1
Ministry of Agriculture Laboratory of Quality & Safety Risk Assessment for Dairy Products (Beijing), Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
2
Ministry of Agriculture—Milk and Dairy Product Inspection Center (Beijing), Beijing 100193, China
3
State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Christo Z. Christov
Int. J. Mol. Sci. 2016, 17(7), 1078; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17071078
Received: 13 May 2016 / Revised: 19 June 2016 / Accepted: 29 June 2016 / Published: 19 July 2016
Targeting threonyl-tRNA synthetase (ThrRS) of Brucella abortus is a promising approach to developing small-molecule drugs against bovine brucellosis. Using the BLASTp algorithm, we identified ThrRS from Escherichia coli (EThrRS, PDB ID 1QF6), which is 51% identical to ThrRS from Brucella abortus (BaThrRS) at the amino acid sequence level. EThrRS was used as the template to construct a BaThrRS homology model which was optimized using molecular dynamics simulations. To determine the residues important for substrate ATP binding, we identified the ATP-binding regions of BaThrRS, docked ATP to the protein, and identified the residues whose side chains surrounded bound ATP. We then used the binding site of ATP to virtually screen for BaThrRS inhibitors and got seven leads. We further characterized the BaThrRS-binding site of the compound with the highest predicted inhibitory activity. Our results should facilitate future experimental effects to find novel drugs for use against bovine brucellosis. View Full-Text
Keywords: bovine brucellosis; homology modeling; molecular dynamics; virtual screening; docking bovine brucellosis; homology modeling; molecular dynamics; virtual screening; docking
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MDPI and ACS Style

Li, M.; Wen, F.; Zhao, S.; Wang, P.; Li, S.; Zhang, Y.; Zheng, N.; Wang, J. Exploring the Molecular Basis for Binding of Inhibitors by Threonyl-tRNA Synthetase from Brucella abortus: A Virtual Screening Study. Int. J. Mol. Sci. 2016, 17, 1078. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17071078

AMA Style

Li M, Wen F, Zhao S, Wang P, Li S, Zhang Y, Zheng N, Wang J. Exploring the Molecular Basis for Binding of Inhibitors by Threonyl-tRNA Synthetase from Brucella abortus: A Virtual Screening Study. International Journal of Molecular Sciences. 2016; 17(7):1078. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17071078

Chicago/Turabian Style

Li, Ming, Fang Wen, Shengguo Zhao, Pengpeng Wang, Songli Li, Yangdong Zhang, Nan Zheng, and Jiaqi Wang. 2016. "Exploring the Molecular Basis for Binding of Inhibitors by Threonyl-tRNA Synthetase from Brucella abortus: A Virtual Screening Study" International Journal of Molecular Sciences 17, no. 7: 1078. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17071078

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