Plasmodium vivax hypoxanthine-guanine phosphoribosyltransferase (PvHGPRT)

Plasmodium vivax hypoxanthine-guanine phosphoribosyltransferase (PvHGPRT) is an essential enzyme for the survival and replication of the malaria parasite Plasmodium vivax (UniProt: A5K701). Since Plasmodium species are unable to synthesize purine nucleotides de novo, they depend entirely on the purine salvage pathway to obtain these vital components for DNA and RNA synthesis (PubMed: 19103608). PvHGPRT facilitates this by converting hypoxanthine, guanine, and xanthine into their corresponding nucleoside monophosphates (PubMed: 25613155). This metabolic dependency makes PvHGPRT an attractive therapeutic target, as its inhibition effectively starves the parasite of the building blocks needed for growth (PubMed: 22409550). Current drug discovery efforts focus on acyclic nucleoside phosphonates (ANPs) that mimic the enzyme's transition state or substrates to achieve high-affinity binding (PubMed: 28640571). A key challenge in targeting PvHGPRT is ensuring high selectivity to avoid inhibiting the human HGPRT ortholog, which could lead to adverse effects such as hyperuricemia or neurological symptoms (PubMed: 25613155).

Other names

Hypoxanthine-guanine phosphoribosyltransferasePlasmodium vivax hypoxanthine–guanine phosphoribosyltransferasePvHPRTHGPRTHPRTP. vivax HGPRT

Competitive inhibition of the purine salvage pathway, specifically blocking the conversion of purine bases into nucleotides, which prevents parasite DNA and RNA synthesis (PubMed: 28640571).