An Antifungal Agent Inhibits an Aminoacyl-tRNA Synthetase by Trapping tRNA in the Editing Site
Shanghai Jiao Tong University · European Molecular Biology Laboratory · +2 more institutions
Abstract
Aminoacyl-transfer RNA (tRNA) synthetases, which catalyze the attachment of the correct amino acid to its corresponding tRNA during translation of the genetic code, are proven antimicrobial drug targets. We show that the broad-spectrum antifungal 5-fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole (AN2690), in development for the treatment of onychomycosis, inhibits yeast cytoplasmic leucyl-tRNA synthetase by formation of a stable tRNA(Leu)-AN2690 adduct in the editing site of the enzyme. Adduct formation is mediated through the boron atom of AN2690 and the 2'- and 3'-oxygen atoms of tRNA's3'-terminal adenosine. The trapping of enzyme-bound tRNA(Leu) in the editing site prevents catalytic turnover, thus…
Citation impact
- FWCI
- 8.61
- Percentile
- 100%
- References
- 13
Authors
16- FRFernando RockCorresponding
Shanghai Jiao Tong University, European Molecular Biology Laboratory, Institute of Molecular Biology and Genetics, Stanford University
- WMWeimin MaoCorresponding
Shanghai Jiao Tong University, European Molecular Biology Laboratory, Institute of Molecular Biology and Genetics, Stanford University
- AYA. Yaremchuk
Shanghai Jiao Tong University, European Molecular Biology Laboratory, Institute of Molecular Biology and Genetics, Stanford University
- MAM. A. Tukalo
Shanghai Jiao Tong University, European Molecular Biology Laboratory, Institute of Molecular Biology and Genetics, Stanford University
- TCThibaut Crépin
Shanghai Jiao Tong University, European Molecular Biology Laboratory, Institute of Molecular Biology and Genetics, Stanford University
Topics & keywords
- Transfer RNA
- Aminoacyl tRNA synthetase
- Genetic code
- Biochemistry
- Enzyme
- Amino Acyl-tRNA Synthetases
- Translation (biology)
- Aminoacylation