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Full-Text Articles in Physical Sciences and Mathematics
Discovery And Characterization Of Chemical Compounds That Inhibit The Function Of Aspartyl-Trna Synthetase From Pseudomonas Aeruginosa, Araceli Corona, Stephanie O. Palmer, Regina Zamacona, Benjamin Mendez, Frank B. Dean, James M. Bullard
Discovery And Characterization Of Chemical Compounds That Inhibit The Function Of Aspartyl-Trna Synthetase From Pseudomonas Aeruginosa, Araceli Corona, Stephanie O. Palmer, Regina Zamacona, Benjamin Mendez, Frank B. Dean, James M. Bullard
Chemistry Faculty Publications and Presentations
Pseudomonas aeruginosa, an opportunistic pathogen, is highly susceptible to developing resistance to multiple antibiotics. The gene encoding aspartyl-tRNA synthetase (AspRS) from P. aeruginosa was cloned and the resulting protein characterized. AspRS was kinetically evaluated, and the KM values for aspartic acid, ATP, and tRNA were 170, 495, and 0.5 μM, respectively. AspRS was developed into a screening platform using scintillation proximity assay (SPA) technology and used to screen 1690 chemical compounds, resulting in the identification of two inhibitory compounds, BT02A02 and BT02C05. The minimum inhibitory concentrations (MICs) were determined against nine clinically relevant bacterial strains, including efflux pump …
Identification Of Chemical Compounds That Inhibit The Function Of Histidyl-Trna Synthetase From Pseudomonas Aeruginosa, Yanmei Hu, Stephanie O. Palmer, Sara Robles, Tahyra Resto, Frank Dean, James M. Bullard
Identification Of Chemical Compounds That Inhibit The Function Of Histidyl-Trna Synthetase From Pseudomonas Aeruginosa, Yanmei Hu, Stephanie O. Palmer, Sara Robles, Tahyra Resto, Frank Dean, James M. Bullard
Chemistry Faculty Publications and Presentations
Pseudomonas aeruginosa histidyl-tRNA synthetase (HisRS) was selected as a target for antibiotic drug development. The HisRS protein was overexpressed in Escherichia coli and kinetically evaluated. The KM values for interaction of HisRS with its three substrates, histidine, ATP, and tRNAHis, were 37.6, 298.5, and 1.5 μM, while the turnover numbers were 8.32, 16.8, and 0.57 s-1, respectively. A robust screening assay was developed, and 800 natural products and 890 synthetic compounds were screened for inhibition of activity. Fifteen compounds with inhibitory activity were identified, and the minimum inhibitory concentration (MIC) was determined for each against a panel of nine pathogenic …