The L.donovani Hypoxanthine-guanine phosphoribosyl transferase (HGPRT) oligomer is distinct from the human homolog.

ABSTRACT

Purine bases, synthesized de novo or recycled through the salvage pathway, are precursors of nucleotide synthesis and are essential in a variety of physiological processes including cell division, growth, signaling, energy metabolism and synthesis of vitamins/co-factor. The protozoan kinetoplastid parasites including Leishmania cannot synthesize de novo and rely solely on the purine salvage pathway, recycling the degraded products of nucleic acid metabolism. Enzymes of this pathway are thus of therapeutic importance. The enzyme Hypoxanthine-guanine phosphoribosyl transferase (HGPRT) (EC 2.4.2.8) plays a central role in this pathway, converting the purine base to its monophosphate product. Towards the elucidation of its role, we have cloned, expressed, purified and determined the crystal structure of L. donovani HGPRT at 2.76 Å. Comparative structural analysis with the human homolog indicates differences in oligomer association. Comparative analyses identify insertions in the human homolog sequence in the tetramer interface. The results suggest that this difference can be exploited for therapeutic approaches.