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Target id: 3077
Nomenclature: Plasmodium falciparum purine nucleoside phosphorylase
Abbreviated Name: PfPNP
Family: Nucleoside synthesis and metabolism (Plasmodium spp.)
Gene and Protein Information | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Plasmodium falciparum 3D7 | - | 245 | PNP | purine nucleoside phosphorylase |
Previous and Unofficial Names |
PNP | Pf3D7_05_v3:568,594..570,527(-) | PFE0660c |
Database Links | |
Alphafold | Q8I3X4 (Pf3D7) |
ChEMBL Target | CHEMBL4523389 (Pf3D7) |
PlasmoDB | PF3D7_0513300 (Pf3D7) |
UniProtKB | Q8I3X4 (Pf3D7) |
Selected 3D Structures | |||||||||||||
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Download all structure-activity data for this target as a CSV file
Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Whole Organism Assay Data Linked to This Target | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Malaria Pharmacology Comments |
Protozoan parasites, including Plasmodium spp., are unable to synthesize purines de novo and instead salvage and recycle these molecules from the host. P. falciparum purine nucleoside phosphorylase (PfPNP), an enzyme involved in the nucleotide salvage pathway is inhibited by several compounds with antimalarial activity. Immucillins are inhibitors of both mammalian PNP and PfPNP, leading to death of the malaria parasite in culture and in an animal model of the disease [1,3-4,6]. PfPNP has also been shown to be the common binding target for mefloquine and quinine, two approved antimalarial drugs from the same chemical class and with complex and poorly understood MoAs [2]. The high affinity interaction for quinine indicates that inhibition of PfPNP may be of clinical relevance. |
1. Cassera MB, Hazleton KZ, Merino EF, Obaldia 3rd N, Ho MC, Murkin AS, DePinto R, Gutierrez JA, Almo SC, Evans GB et al.. (2011) Plasmodium falciparum parasites are killed by a transition state analogue of purine nucleoside phosphorylase in a primate animal model. PLoS ONE, 6 (11): e26916. [PMID:22096507]
2. Dziekan JM, Yu H, Chen D, Dai L, Wirjanata G, Larsson A, Prabhu N, Sobota RM, Bozdech Z, Nordlund P. (2019) Identifying purine nucleoside phosphorylase as the target of quinine using cellular thermal shift assay. Sci Transl Med, 11 (473). [PMID:30602534]
3. Kicska GA, Tyler PC, Evans GB, Furneaux RH, Kim K, Schramm VL. (2002) Transition state analogue inhibitors of purine nucleoside phosphorylase from Plasmodium falciparum. J Biol Chem, 277 (5): 3219-25. [PMID:11707439]
4. Kicska GA, Tyler PC, Evans GB, Furneaux RH, Schramm VL, Kim K. (2002) Purine-less death in Plasmodium falciparum induced by immucillin-H, a transition state analogue of purine nucleoside phosphorylase. J Biol Chem, 277 (5): 3226-31. [PMID:11706018]
5. Shi W, Ting LM, Kicska GA, Lewandowicz A, Tyler PC, Evans GB, Furneaux RH, Kim K, Almo SC, Schramm VL. (2004) Plasmodium falciparum purine nucleoside phosphorylase: crystal structures, immucillin inhibitors, and dual catalytic function. J Biol Chem, 279 (18): 18103-6. [PMID:14982926]
6. Ting LM, Shi W, Lewandowicz A, Singh V, Mwakingwe A, Birck MR, Ringia EA, Bench G, Madrid DC, Tyler PC et al.. (2005) Targeting a novel Plasmodium falciparum purine recycling pathway with specific immucillins. J Biol Chem, 280 (10): 9547-54. [PMID:15576366]
Nucleoside synthesis and metabolism (Plasmodium spp.): Plasmodium falciparum purine nucleoside phosphorylase. Last modified on 12/10/2021. Accessed on 15/11/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=3077.