ArticleCurrent drug discovery technologies2014
High Throughput Screen Identifies Natural Product Inhibitor of Phenylalanyl-tRNA Synthetase from Pseudomonas aeruginosa and Streptococcus pneumoniae.
Article in Current drug discovery technologies, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- Mycobacterium tuberculosis Phe-tRNA synthetase: structural insights into tRNA recognition and aminoacylation.Nucleic acids research · 2021Article
- Thioredoxin Reductase Is a Valid Target for Antimicrobial Therapeutic Development Against Gram-Positive Bacteria.Frontiers in microbiology · 2021Article
- Two Forms of Tyrosyl-tRNA Synthetase fromSLAS discovery : advancing life sciences R & D · 2020Article
- Lysyl-tRNA Synthetase fromSLAS discovery : advancing life sciences R & D · 2020Article
- Progress and challenges in aminoacyl-tRNA synthetase-based therapeutics.The Journal of biological chemistry · 2019Review
- Characterization and structure determination of prolyl-tRNA synthetase from Pseudomonas aeruginosa and development as a screening platform.Protein science : a publication of the Protein Society · 2019Article
- Identification of Chemical Compounds That Inhibit the Function of Histidyl-tRNA Synthetase from Pseudomonas aeruginosa.SLAS discovery : advancing life sciences R & D · 2018Article
- Identification of Chemical Compounds That Inhibit Protein Synthesis in Pseudomonas aeruginosa.SLAS discovery : advancing life sciences R & D · 2017Article
- Identification and Characterization of a Chemical Compound that Inhibits Methionyl-tRNA Synthetase from Pseudomonas aeruginosa.Current drug discovery technologies · 2017Article
- Discovery and Analysis of Natural-Product Compounds Inhibiting Protein Synthesis in Pseudomonas aeruginosa.Antimicrobial agents and chemotherapy · 2016Article
- Aminoacyl-tRNA Synthetases in the Bacterial World.EcoSal Plus · 2016Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Pseudomonas aeruginosa and Streptococcus pneumoniae are causative agents in a wide range of infections. Genes encoding proteins corresponding to phenylalanyl-tRNA synthetase (PheRS) were cloned from both bacteria. The two forms of PheRS were kinetically evaluated and the K(m)'s for P. aeruginosa PheRS with its three substrates, phenylalanine, ATP and tRNA(Phe) were determined to be 48, 200, and 1.2 µM, respectively, while the K(m)'s for S. pneumoniae PheRS with respect to phenylalanine, ATP and tRNA(Phe) were 21, 225 and 0.94 µM, respectively. P. aeruginosa and S. pneumoniae PheRS were used to screen a natural compound library and a single compound was identified that inhibited the function of both enzymes. The compound inhibited P. aeruginosa and S. pneumoniae PheRS with IC50's of 2.3 and 4.9 µM, respectively. The compound had a K(I) of 0.83 and 0.98 µM against P. aeruginosa and S. pneumoniae PheRS, respectively. The minimum inhibitory concentration (MIC) of the compound was determined against a panel of Gram positive and negative bacteria including efflux pump mutants and hyper-sensitive strains. MICs against wild-type P. aeruginosa and S. pneumoniae cells in culture were determined to be 16 and 32 µg/ml, respectively. The mechanism of action of the compound was determined to be competitive with the amino acid, phenylalanine, and uncompetitive with ATP. There was no inhibition of cytoplasmic protein synthesis, however, partial inhibition of the human mitochondrial PheRS was observed.
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Registered trials
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