Structure-function Relationships in Human Hypoxanthine- guanine Phosphoribosyltransferase (HGPRT) by Random Mutagenesis

摘要

Hypoxanthine-guanine phosphoribosyltransferase ( HGPRT, EC 2.4. 2.8) is a key enzyme of the purine salvage pathway, which allows recycling of purine bases into DNA and RNA. It is widely distributed in nature and has been studied both in prokaryotes and eu-karyotes. In humans, a complete lack of HGPRT activity causes the Lesch-Nyhan syndrome, which is characterized by hyperuricaemia and neural disorders, including mental retardation and compulsive self-mutilation behavior . Partial deficiency of HGPRT activity may lead to gouty arthritis. Many parasites, such as Plas-modium falciparum, lack de novo purine nucleotide synthesis and make purine nucleotides only through salvage pathways. Hence, enzymes in salvage pathways are potential targets of therapeutic agents for treatment of parasitic diseases.