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BioAssay: AID 289193

Inhibition of Saccharomyces cerevisiae cytoplasmic leucyl-tRNA synthetase assessed as tRNA amino-acylation

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 more ..
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 Tested Compounds
 Tested Compounds
All(7)
 
 
Active(1)
 
 
Unspecified(6)
 
 
 Tested Substances
 Tested Substances
All(7)
 
 
Active(1)
 
 
Unspecified(6)
 
 
 Related BioAssays
 Related BioAssays
AID: 289193
Data Source: ChEMBL (437219)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-25
Modify Date: 2013-11-19

Data Table ( Complete ):           Active    All
Target
Sequence: RecName: Full=Leucine--tRNA ligase, cytoplasmic; AltName: Full=Leucyl-tRNA synthetase; Short=LeuRS
Description ..   
Protein Family: catalytic core domain of leucyl-tRNA synthetases
Comment ..   

Gene:CDC60     Related Protein 3D Structures     More BioActivity Data..
BioActive Compound: 1
Description:
Title: An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site.

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.
(PMID: 17588934)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Categorized Comment
ChEMBL Assay Type: Binding

ChEMBL Assay Data Source: Scientific Literature

ChEMBL Target ID: 102960

ChEMBL Target Type: Target is a single protein chain

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
2IC50 activity commentIC50 activity commentString
3IC50 standard flagIC50 standard flagInteger
4IC50 qualifierIC50 qualifierString
5IC50 published valueIC50 published valueFloatμM
6IC50 standard valueIC50 standard valueFloatnM

* Activity Concentration.

Data Table (Concise)
Classification
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