Purine salvage pathway enzymes from Helicobacter pylori and Escherichia coli
The main goal of the proposed project is to identify new drug targets and accordingly design, prepare and characterise new drugs for Helicobacter pylori eradication. Helicobacter pylori is a bacterium that colonizes one half of the world population and it is regarded as one of the most invasive human pathogens responsible for development of many diseases. There are two possible pathways that organisms can use to synthesize purines as indispensable building blocks for DNA and RNA synthesis. However, bacterium H. pylori uses the salvage pathway, only. Therefore, we plan to disable H. pylori growth and replication by inhibiting the key enzymes, purine nucleoside phosphorylase and adenylosuccinate synthetase, on this pathway. The proposed project includes the interdisciplinary team with expertise in the research areas of molecular biology and genetics, biochemistry and biophysics, macromolecular crystallography, biological mass spectrometry, molecular modelling, organic synthesis, analytical ultracentrifugation methods, susceptibility testing, and managing ‘big data’ through data integration (extracted from various databases). All equipment necessary to accomplish the proposed research is available in the host institution (Rudjer Bošković Institute) except for analytical ultracentrifuge available by foreign co-worker A. Bzowska (Warsaw, Poland).