Purine nucleoside phosphorylase (Plasmodium falciparum) (PfPNP)

Purine nucleoside phosphorylase (PfPNP) from Plasmodium falciparum is an essential enzyme in the parasite’s purine salvage pathway. P. falciparum is a purine auxotroph and relies entirely on salvaging purines from its host for nucleic acid synthesis. PfPNP catalyzes the reversible phosphorolysis of N-glycosidic bonds in 6-oxopurine (deoxy)ribonucleosides to produce hypoxanthine and ribose 1-phosphate. Hypoxanthine is an essential precursor for all purines required for DNA/RNA synthesis in P. falciparum. Transition state analog inhibitors such as DADMe-Immucillin-G potently inhibit both human and malarial PNPs and can clear infections in animal models by inducing lethal purine starvation in parasites. Resistance can arise via gene amplification or point mutations affecting inhibitor binding but often at significant cost to catalytic efficiency.

Other names

P. falciparum PNPPfPNPPFE0660c

Transition state analog inhibition