Evolutionary Limitation and Opportunities for Developing tRNA Synthetase Inhibitors with 5-Binding-Mode Classification
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 s...
Main Authors: | , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2015-12-01
|
Series: | Life |
Subjects: | |
Online Access: | http://www.mdpi.com/2075-1729/5/4/1703 |
id |
doaj-15f313c68a73404ab940fd8890567a95 |
---|---|
record_format |
Article |
spelling |
doaj-15f313c68a73404ab940fd8890567a952020-11-25T00:01:36ZengMDPI AGLife2075-17292015-12-01541703172510.3390/life5041703life5041703Evolutionary Limitation and Opportunities for Developing tRNA Synthetase Inhibitors with 5-Binding-Mode ClassificationPengfei Fang0Min Guo1State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, ChinaDepartment of Cancer Biology, The Scripps Research Institute, Scripps Florida, 130 Scripps Way, Jupiter, FL 33458, USAAminoacyl-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.http://www.mdpi.com/2075-1729/5/4/1703aminoacyl-tRNA synthetase (aaRS)inhibitorevolutionprotein-ligand interactionstructure conservationspecies specificity |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pengfei Fang Min Guo |
spellingShingle |
Pengfei Fang Min Guo Evolutionary Limitation and Opportunities for Developing tRNA Synthetase Inhibitors with 5-Binding-Mode Classification Life aminoacyl-tRNA synthetase (aaRS) inhibitor evolution protein-ligand interaction structure conservation species specificity |
author_facet |
Pengfei Fang Min Guo |
author_sort |
Pengfei Fang |
title |
Evolutionary Limitation and Opportunities for Developing tRNA Synthetase Inhibitors with 5-Binding-Mode Classification |
title_short |
Evolutionary Limitation and Opportunities for Developing tRNA Synthetase Inhibitors with 5-Binding-Mode Classification |
title_full |
Evolutionary Limitation and Opportunities for Developing tRNA Synthetase Inhibitors with 5-Binding-Mode Classification |
title_fullStr |
Evolutionary Limitation and Opportunities for Developing tRNA Synthetase Inhibitors with 5-Binding-Mode Classification |
title_full_unstemmed |
Evolutionary Limitation and Opportunities for Developing tRNA Synthetase Inhibitors with 5-Binding-Mode Classification |
title_sort |
evolutionary limitation and opportunities for developing trna synthetase inhibitors with 5-binding-mode classification |
publisher |
MDPI AG |
series |
Life |
issn |
2075-1729 |
publishDate |
2015-12-01 |
description |
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. |
topic |
aminoacyl-tRNA synthetase (aaRS) inhibitor evolution protein-ligand interaction structure conservation species specificity |
url |
http://www.mdpi.com/2075-1729/5/4/1703 |
work_keys_str_mv |
AT pengfeifang evolutionarylimitationandopportunitiesfordevelopingtrnasynthetaseinhibitorswith5bindingmodeclassification AT minguo evolutionarylimitationandopportunitiesfordevelopingtrnasynthetaseinhibitorswith5bindingmodeclassification |
_version_ |
1725441170571526144 |