Back to Search
Start Over
Aminoacyl-tRNA Synthetases as Valuable Targets for Antimicrobial Drug Discovery.
- 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.
- Subjects :
- Amino Acids metabolism
Amino Acyl-tRNA Synthetases chemistry
Amino Acyl-tRNA Synthetases metabolism
Animals
Anti-Infective Agents chemistry
Binding Sites drug effects
Enzyme Inhibitors chemistry
Humans
Models, Molecular
Molecular Targeted Therapy
Amino Acyl-tRNA Synthetases antagonists & inhibitors
Anti-Infective Agents pharmacology
Drug Discovery
Enzyme Inhibitors pharmacology
Subjects
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