Helicobacter pylori is one of the most common bacterial infections; over two-thirds of the world's population is infected by early childhood. Persistent H. pylori infection results in gastric ulcers and cancers. Due to drug resistance, there is a need to develop alternative treatments to clear H. pylori. The Seattle Structural Genomics Center for Infectious Disease (SSGCID) conducts structure-function analysis of potential therapeutic targets from H. pylori. Glutamyl-tRNA synthetase (GluRS) is essential for tRNA aminoacylation and is under investigation as a bacterial drug target. The SSGCID produced, crystallized and determined the apo structure of H. pylori GluRS (HpGluRS). HpGluRS has the prototypical bacterial GluRS topology and has similar binding sites and tertiary structures to other bacterial GluRS that are promising drug targets. Residues involved in glutamate binding are well conserved in comparison with Pseudomonas aeruginosa GluRS (PaGluRS), which has been studied to develop promising new inhibitors for P. aeruginosa. These structural similarities can be exploited for drug discovery and repurposing to generate new antibacterials to clear persistent H. pylori infection and reduce gastric ulcers and cancer.
Keywords: Seattle Structural Genomics Center for Infectious Disease; cancer; gastric ulcers; glutamyl-tRNA synthetase; infectious diseases; undergraduate education and training.
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