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Aminoacyl-tRNA Synthetases as Valuable Targets for Antimicrobial Drug Discovery.

Authors :
Pang L
Weeks SD
Van Aerschot A
Source :
International journal of molecular sciences [Int J Mol Sci] 2021 Feb 10; Vol. 22 (4). Date of Electronic Publication: 2021 Feb 10.
Publication Year :
2021

Abstract

Aminoacyl-tRNA synthetases (aaRSs) catalyze the esterification of tRNA with a cognate amino acid and are essential enzymes in all three kingdoms of life. Due to their important role in the translation of the genetic code, aaRSs have been recognized as suitable targets for the development of small molecule anti-infectives. In this review, following a concise discussion of aaRS catalytic and proof-reading activities, the various inhibitory mechanisms of reported natural and synthetic aaRS inhibitors are discussed. Using the expanding repository of ligand-bound X-ray crystal structures, we classified these compounds based on their binding sites, focusing on their ability to compete with the association of one, or more of the canonical aaRS substrates. In parallel, we examined the determinants of species-selectivity and discuss potential resistance mechanisms of some of the inhibitor classes. Combined, this structural perspective highlights the opportunities for further exploration of the aaRS enzyme family as antimicrobial targets.

Details

Language :
English
ISSN :
1422-0067
Volume :
22
Issue :
4
Database :
MEDLINE
Journal :
International journal of molecular sciences
Publication Type :
Academic Journal
Accession number :
33578647
Full Text :
https://doi.org/10.3390/ijms22041750