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Int. J. Mol. Sci. 2016, 17(7), 1078; doi:10.3390/ijms17071078

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

1,2,†
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1,2,†
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1,2,†
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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
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Christo Z. Christov
Received: 13 May 2016 / Revised: 19 June 2016 / Accepted: 29 June 2016 / Published: 19 July 2016
View Full-Text   |   Download PDF [6654 KB, uploaded 19 July 2016]   |  

Abstract

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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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.

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