Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:6.1.1.4 (
leucyl-tRNA synthetase
)
297
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The broad-spectrum benzoxaborole antifungal AN2690 blocks protein synthesis by inhibiting
leucyl-tRNA synthetase
(
LeuRS
) via a novel oxaborole tRNA trapping mechanism in the editing site. Herein, one set of resistance mutations is at Asp487 outside the
LeuRS
hydrolytic editing pocket, in a region of unknown function. It is located within a eukaryote/archaea specific insert I4, which forms part of a cap over a benzoxaborole-AMP that is bound in the
LeuRS
CP1 domain editing active site. Mutational and biochemical analysis at Asp487 identified a
salt
bridge between Asp487 and Arg316 in the hinge region of the I4 cap of yeast
LeuRS
that is critical for tRNA deacylation. We hypothesize that this electrostatic interaction stabilizes the cap during binding of the editing substrate for hydrolysis.
...
PMID:Characterization of benzoxaborole-based antifungal resistance mutations demonstrates that editing depends on electrostatic stabilization of the leucyl-tRNA synthetase editing cap. 2185 1
