Characterizing Arginyl-tRNA from Prevotella intermedia for Drug Design
Abstract
Antibiotic resistance is becoming more prevalent; thus, the need to find other inhibition pathways. A possibility is the aminoacyl-tRNA synthetases which catalyze the attachment of the amino acid to its respective tRNA. These enzymes are an excellent target for drug development. Prevotella intermedia (Pi) is an orphan organism which causes Noma, an oral cavity flesh-eating disease. We selected the Pi arginyl-tRNA synthetase (ArgRS) because of its unusual features and dissimilarity to human homologs. More so, we are characterizing the ArgRS’s ability to bind tRNA and arginine as a prelude to drug design. Gel shift assays and aminoacylation assays will be used to characterize the interaction of the enzyme with tRNA and arginine. Once the enzymatic characterization is complete, we will pursue potential drugs, which include modified arginines. This work will lead to a better understanding of the interaction of the tRNA and arginine with the synthetase and will help computational work to determine a suitable inhibitor. By designing drugs against the tRNA synthetases, we can expand a powerful new class of antibiotics.
Characterizing Arginyl-tRNA from Prevotella intermedia for Drug Design
Antibiotic resistance is becoming more prevalent; thus, the need to find other inhibition pathways. A possibility is the aminoacyl-tRNA synthetases which catalyze the attachment of the amino acid to its respective tRNA. These enzymes are an excellent target for drug development. Prevotella intermedia (Pi) is an orphan organism which causes Noma, an oral cavity flesh-eating disease. We selected the Pi arginyl-tRNA synthetase (ArgRS) because of its unusual features and dissimilarity to human homologs. More so, we are characterizing the ArgRS’s ability to bind tRNA and arginine as a prelude to drug design. Gel shift assays and aminoacylation assays will be used to characterize the interaction of the enzyme with tRNA and arginine. Once the enzymatic characterization is complete, we will pursue potential drugs, which include modified arginines. This work will lead to a better understanding of the interaction of the tRNA and arginine with the synthetase and will help computational work to determine a suitable inhibitor. By designing drugs against the tRNA synthetases, we can expand a powerful new class of antibiotics.