In:
Science, American Association for the Advancement of Science (AAAS), Vol. 316, No. 5832 ( 2007-06-22), p. 1759-1761
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 inhibiting synthesis of leucyl-tRNA Leu and consequentially blocking protein synthesis. This result establishes the editing site as a bona fide target for aminoacyl-tRNA synthetase inhibitors.
Type of Medium:
Online Resource
ISSN:
0036-8075
,
1095-9203
DOI:
10.1126/science.1142189
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2007
detail.hit.zdb_id:
128410-1
detail.hit.zdb_id:
2066996-3
detail.hit.zdb_id:
2060783-0
SSG:
11
