Plasmodium hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT)

Hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) from Plasmodium species (including *Plasmodium vivax* and *Plasmodium falciparum*) is an essential enzyme required for the salvage of purine bases hypoxanthine, guanine, and xanthine to their respective nucleotides (IMP, GMP, and XMP) in the malaria parasite[1][2][4]. The enzyme catalyzes the transfer of a ribosyl phosphate group from 5-phosphoribose 1-diphosphate (PRPP) to N(9) of these bases. Since Plasmodium parasites are purine auxotrophs and cannot synthesize purines de novo, they rely heavily on this salvage pathway to maintain their nucleotide pools necessary for DNA/RNA synthesis and survival in erythrocytes[2][3][4]. Inhibition of HGXPRT leads to purine starvation and parasite death, making it a validated antimalarial drug target[2][4]. Transition state analogue inhibitors and prodrugs targeting HGXPRT have demonstrated potent parasite killing in culture and animal models[2][4]. The enzyme is fully cytoplasmic and structurally characterized, with no evidence for it being a receptor, ion channel, or transporter[1][7].

Other names

Hypoxanthine-guanine-xanthine phosphoribosyltransferaseHGPRT2.4.2.22

Inhibition of enzymatic activity needed for purine salvage, resulting in parasite purine starvation