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Life 2015, 5(4), 1703-1725; doi:10.3390/life5041703

Evolutionary Limitation and Opportunities for Developing tRNA Synthetase Inhibitors with 5-Binding-Mode Classification

1,2
and
2,*
1
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
2
Department of Cancer Biology, The Scripps Research Institute, Scripps Florida, 130 Scripps Way, Jupiter, FL 33458, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Lluís Ribas de Pouplana and Adrian Gabriel Torres
Received: 1 November 2015 / Revised: 24 November 2015 / Accepted: 25 November 2015 / Published: 8 December 2015
(This article belongs to the Special Issue Evolution of tRNA)
View Full-Text   |   Download PDF [2840 KB, uploaded 8 December 2015]   |  

Abstract

Aminoacyl-tRNA synthetases (aaRSs) are enzymes that catalyze the transfer of amino acids to their cognate tRNAs as building blocks for translation. Each of the aaRS families plays a pivotal role in protein biosynthesis and is indispensable for cell growth and survival. In addition, aaRSs in higher species have evolved important non-translational functions. These translational and non-translational functions of aaRS are attractive for developing antibacterial, antifungal, and antiparasitic agents and for treating other human diseases. The interplay between amino acids, tRNA, ATP, EF-Tu and non-canonical binding partners, had shaped each family with distinct pattern of key sites for regulation, with characters varying among species across the path of evolution. These sporadic variations in the aaRSs offer great opportunity to target these essential enzymes for therapy. Up to this day, growing numbers of aaRS inhibitors have been discovered and developed. Here, we summarize the latest developments and structural studies of aaRS inhibitors, and classify them with distinct binding modes into five categories. View Full-Text
Keywords: aminoacyl-tRNA synthetase (aaRS); inhibitor; evolution; protein-ligand interaction; structure conservation; species specificity aminoacyl-tRNA synthetase (aaRS); inhibitor; evolution; protein-ligand interaction; structure conservation; species specificity
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Fang, P.; Guo, M. Evolutionary Limitation and Opportunities for Developing tRNA Synthetase Inhibitors with 5-Binding-Mode Classification. Life 2015, 5, 1703-1725.

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