REGULATION OF CELLULAR NUCLEOTIDE POOLS (UDP AND PNP)

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Uridine Phosphorylase (UP) is a key enzyme in the pyrimidine salvage pathway. It catalyses the reversible phosphorolysis of uridine to uracil and ribose-1-phosphate. It is a member of the large nucleoside phosphorylase I super family of enzymes. The inhibition of UP in human increases blood uridine levels and produces a protective effect against the toxicity of the chemotherapeutic agent 5-fluorouracil without reducing its antitumour activity. Present studies are focused on structural characterization and mechanistic understanding of bovine uridine phosphorylaseand the design of new inhibitors. Purine nucleoside phosphorylase (PNP) catalyzes the reversible phosphorolysis of purine ribonucleosides to corresponding free bases and ribose 1-phosphate. Depending on structure and substrate specificity, PNPs are divided into two classes: low-molecular-mass homotrimers, mainly found in mammals and high-molecular-mass homohexamers, found in microorganisms. The enzyme activity is stimulated by ATP and suppressed by phosphate and has been detected in prokaryotes. PNPs are attractive targets for the design of antimicrobial drugs and chemotherapeutic drugs.