The purine nucleotides play a key role in synthesis of DNA, RNA and ATP supply. Living organisms can produce purine nucleotides de novo or via the salvage pathway. Two pathways are inter-related, share alpha-D-phosphoribosyl-1-pyrophosphate (PRPP) as a common substrate and may impose regulation on each other. Many pathogenic organisms are deficient in de novo synthesis of the purine nucleotides, and therefore must rely on the salvage pathway. The key enzyme in the latter pathway is a hypoxanthine-guanine phosphoribosyltransferase (HGPRT, E.C. 126.96.36.199), which catalyzes a reversible transfer of the 5-phosphoribosyl group from PRPP to the N9 atom of either hypoxanthine or guanine to form inosine 5''-monophosphate (IMP) or guanosine 5''-monophosphate (GMP), respectively. It is of scientific and medical interest to understand the mechanism of the HGPRT-catalyzed reaction, because it will help to develop inhibition strategies of the enzyme, and hence create therapeutic agents for treatment of diseases caused by human pathogens.
We have determined crystal structure of apo-IDP01634 and refined it to 1.98 A resolution. In the PRPP binding site of IDP01634, sulfate ions and glycerol molecules were modeled.