ENZYMES OF PURINE SALVAGE

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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. Purines are essential molecules for many cellular processes including nucleic acid and nucleotide metabolism, energy transfer and storage, protein synthesis and signaling. In addition, some organisms can utilize purines as a nitrogen source when ammonia is absent or limiting. The first step of purine catabolism is a deamination of adenine or guanine to hypoxanthine or xanthine respectively. The remaining catabolic steps can be divided into two parts. The first, common to all species, is the breakdown of (hypo)xanthine to allantoin over several steps by a series of enzymes. The second part of the pathway, the degradation of allantoin to CO2 and ammonia, can vary between microbial species. Recently a set of seven genes responsible for the oxidation of hypoxanthine to allantoin in Klebsiella pneumoniae has been identified. Further work by a different group identified an additional five genes involved in this pathway, including the guanine deaminase and enzymes responsible for the conversion of allantoin to allantoate. The work by these two groups also demonstrated that the cofactors required for the breakdown of xanthine in K. pneumoniae differs from most of the reported xanthine dehydrogenases or oxidoreductases, occurring independently of molybdenum containing enzymes. We have initiated structural studies of several of the enzymes responsible for the catabolism of hypoxanthine in K. pneumoniae.