Crystal structure of glutamyl-tRNA synthetase from Helicobacter pylori
Dr Oluwatoyin A. Asojo [1]
Molecular Tour
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 GluRS (HpGluRS). HpGluRS has the prototypical bacterial GluRS topology, similar binding sites, and tertiary structures with other bacterial GluRS that are promising drug targets. ENDScript[2][3] analysis reveals that HpGluRS is a prototypical bacterial GluRS shown showing sequence conservation as a and Residues involved in glutamate binding are well conserved with Pseudomonas aeruginosa GluRS (PaGluRS), which has been studied to develop promising new inhibitors for Pseudomonas 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.
References
- ↑ doi: https://dx.doi.org/10.1107/S2053230X24011099
- ↑ Gouet P, Robert X, Courcelle E. ESPript/ENDscript: Extracting and rendering sequence and 3D information from atomic structures of proteins. Nucleic Acids Res. 2003 Jul 1;31(13):3320-3. PMID:12824317
- ↑ Robert X, Gouet P. Deciphering key features in protein structures with the new ENDscript server. Nucleic Acids Res. 2014 Jul;42(Web Server issue):W320-4. PMID:24753421 doi:10.1093/nar/gku316
