An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site.

An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site. Research Abstract Details 

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An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site. Abstract Text:

Fernando L Rock,Weimin Mao,Anya Yaremchuk,Mikhail Tukalo,Thibaut ,Huchen Zhou,Yong-Kang Zhang,Vincent Hernandez,Tsutomu Akama,Stephen J Baker,Jacob J Plattner,Lucy Shapiro,Susan A Martinis,Stephen J Benkovic,Stephen Cusack,M R K Alley,

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.

An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site. Publishing Authors By Initials

FL Rock,W Mao,A Yaremchuk,M Tukalo,T ,H Zhou,YK Zhang,V Hernandez,T Akama,SJ Baker,JJ Plattner,L Shapiro,SA Martinis,SJ Benkovic,S Cusack,MR Alley,

For similar fungi: ascomycota: saccharomycetales: saccharomyces: saccharomyces cerevisiae research abstracts see: fungi: ascomycota: saccharomycetales: saccharomyces: saccharomyces cerevisiae research

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An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Science (New York, N.Y.)

VOLUME: 316

Page Numbers: 1759-61

Journal Abbreviation: Science

ISSN: 1095-9203

DAY: 22

MONTH: Jun

YEAR: 2007

An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 404511

An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site. Keywords Mesh Terms:

KEYWORDS: Saccharomyces cerevisiae

MESH TERMS: genetics

Chemical & Substance for Abstract: An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site. Information

Substance Name: Leucine-tRNA Ligase

Registry Number: EC 6.1.1.4

Grant and Affiliation Information for An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site.

AFFILIATION: Anacor Pharmaceuticals, Incorporated, 1060 East Meadow Circle, Palo Alto, CA 94303, USA.

Country: United States

AGENCY: United States NIDCR

GRANT: R01 DE16835

ACRONYM: DE

MEDLINETA: Science

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