2v0g

From Proteopedia

Revision as of 18:14, 18 December 2007

LEUCYL-TRNA SYNTHETASE FROM THERMUS THERMOPHILUS COMPLEXED WITH A TRNA(LEU) TRANSCRIPT WITH 5-FLUORO-1,3-DIHYDRO-1-HYDROXY-2,1-BENZOXABOROLE (AN2690) FORMING AN ADDUCT TO THE RIBOSE OF ADENOSINE-76 IN THE ENZYME EDITING SITE.

Overview

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.

About this Structure

2V0G is a Protein complex structure of sequences from Thermus thermophilus with ZN, HG, SO4 and LEU as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site., Rock FL, Mao W, Yaremchuk A, Tukalo M, Crepin T, Zhou H, Zhang YK, Hernandez V, Akama T, Baker SJ, Plattner JJ, Shapiro L, Martinis SA, Benkovic SJ, Cusack S, Alley MR, Science. 2007 Jun 22;316(5832):1759-61. PMID:17588934

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