Identification and Characterization of Chemical Compounds that Inhibit Leucyl-tRNA Synthetase from Pseudomonas aeruginosa.

ABSTRACT:

Background

Pseudomonas aeruginosa is an opportunistic multi-drug resistance pathogen implicated as the causative agent in a high-percentage of nosocomial and community acquired bacterial infections. The gene encoding leucyl-tRNA synthetase (LeuRS) from P. aeruginosa was overexpressed in Escherichia coli and the resulting protein was characterized.

Methods

LeuRS was kinetically evaluated and the KM values for interactions with leucine, ATP and tRNA were 6.5, 330, and 3.0 μM, respectively. LeuRS was developed into a screening platform using scintillation proximity assay (SPA) technology and used to screen over 2000 synthetic and natural chemical compounds.

Results

The initial screen resulted in the identification of two inhibitory compounds, BT03C09 and BT03E07. IC50s a

SUBMITTER: Zamacona R 

PROVIDER: S-EPMC6367055 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature