Plasmodium falciparum hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase | Antimalarial targets | IUPHAR/MMV Guide to MALARIA PHARMACOLOGY

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Plasmodium falciparum hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase

Target id: 3065

Nomenclature: Plasmodium falciparum hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase

Abbreviated Name: PfPPPK-DHPS

Family: Antimalarial targets

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Plasmodium falciparum 3D7 - 706 PPPK-DHPS hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase
Database Links
PlasmoDB
UniProtKB

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
dapsone Pf Inhibition 5.2 pKi 3
pKi 5.2 (Ki 6x10-6 M) [3]
Description: Enzyme inhibition assay.
Whole Organism Assay Data Linked to This Target
Key to terms and symbols Click column headers to sort
Ligand Sp. Assay description Type Action Value Parameter Reference
sulfadoxine PfHB3 Parasite growth inhibition assay - - 8.4 pIC50 2
pIC50 8.4 (IC50 4x10-9 M) [3H]-hypoxanthine incorporation [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
sulfadoxine Pf3D7 Parasite growth inhibition assay - - 7.1 pIC50 2
pIC50 7.1 (IC50 7.3x10-8 M) [3H]-hypoxanthine incorporation [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
sulfadoxine PfK1 Parasite growth inhibition assay - - 6.7 pIC50 2
pIC50 6.7 (IC50 2.23x10-7 M) [3H]-hypoxanthine incorporation [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
sulfadoxine PfDd2 Parasite growth inhibition assay - - 5.4 pIC50 2
pIC50 5.4 (IC50 3.97x10-6 M) [3H]-hypoxanthine incorporation [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Malaria Pharmacology Comments
The Plasmodium enzyme hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase (PfPPPK-DHPS) is a bifunctional protein involved in the folate biosynthesis pathway and in the mechanism of action of the sulfonamide group of drugs [1].

References

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1. Triglia T, Cowman AF. (1994) Primary structure and expression of the dihydropteroate synthetase gene of Plasmodium falciparum. Proc. Natl. Acad. Sci. U.S.A., 91 (15): 7149-53. [PMID:8041761]

2. Wang P, Read M, Sims PF, Hyde JE. (1997) Sulfadoxine resistance in the human malaria parasite Plasmodium falciparum is determined by mutations in dihydropteroate synthetase and an additional factor associated with folate utilization. Mol. Microbiol., 23 (5): 979-86. [PMID:9076734]

3. Zhang Y, Meshnick SR. (1991) Inhibition of Plasmodium falciparum dihydropteroate synthetase and growth in vitro by sulfa drugs. Antimicrob. Agents Chemother., 35 (2): 267-71. [PMID:2024960]

How to cite this page

Antimalarial targets: Plasmodium falciparum hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase. Last modified on 05/08/2020. Accessed on 25/09/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=3065.