ANNOUNCEMENTS
Helicobacter pylori stands as a predominant human pathogen, significantly linked to a spectrum of gastrointestinal disorders, including gastritis, peptic ulcers, and gastric cancer. Among different virulence factors, phosphatases emerge as pivotal players, orchestrating critical interactions between the pathogen and its host, and pathogenesis. This thesis presents a comprehensive structural characterization of phosphatases from H. pylori, with the primary objective of unraveling their intricate molecular mechanisms and discerning their potential as viable therapeutic targets.
Utilizing a meticulously integrated approach combining structural informatics and X-ray crystallographic techniques, we have delineated the three-dimensional structure of key H. pylori phosphatases. These studies provided insights into the intricate contours of their catalytic cavities, elucidated their mode of action, and determined their substrate specificities. Comparative structural analyses with their homologous phosphatases from diverse organisms have identified distinctive structural attributes and potential vulnerabilities, providing a foundation for targeted therapeutic interventions.
Moreover, our investigations have extended beyond structural elucidation, delving into the functional characterization of H. pylori phosphatases through a gamut of biochemical and biophysical assays. Inhibition kinetics using specific inhibitors have highlighted the putative roles of these phosphatases in modulating host signaling pathways and immune responses, underscoring their importance in H. pylori pathogenesis.
To translate these structural and functional insights into therapeutic avenues, we have conducted an extensive exploration of the druggability of H. pylori phosphatases. Employing a structure-based drug design approach and virtual screening, we have identified and characterized several novel small molecule inhibitors with promising therapeutic potential. These findings lay the groundwork for future drug development aimed at combating H. pylori infections and their associated diseases.
In conclusion, this thesis provides a comprehensive structural and functional framework that enhances our understanding of H. pylori phosphatases. It underscores their potential as compelling targets for therapeutic intervention in H. pylori-associated pathologies, marking a significant step forward against H. pylori.
