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Plasmodium falciparum bifunctional farnesyl/geranylgeranyl diphosphate synthase

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Target id: 3173

Nomenclature: Plasmodium falciparum bifunctional farnesyl/geranylgeranyl diphosphate synthase

Abbreviated Name: PfFPPS/GGPPS

Family: Isoprenoid biosynthesis enzymes

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Plasmodium falciparum 3D7 - 376 FPPS/GGPPS bifunctional farnesyl/geranylgeranyl diphosphate synthase
Previous and Unofficial Names Click here for help
PF11_0295
Database Links Click here for help
Alphafold
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
AIM-1290 Small molecule or natural product Guide to Malaria Pharmacology Ligand Pf Inhibition 5.7 pIC50 3
pIC50 5.7 (IC50 1.94x10-6 M) PfGGPPS enzymatic activity [3]
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
MMV019313 Small molecule or natural product Guide to Malaria Pharmacology Ligand PfDd2 - - 6.7 pEC50 1
pEC50 6.7 (EC50 1.8x10-7 M) [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
MMV019313 Small molecule or natural product Guide to Malaria Pharmacology Ligand PfW2 - - 6.6 pEC50 1
pEC50 6.6 (EC50 2.7x10-7 M) [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
AIM-1290 Small molecule or natural product Guide to Malaria Pharmacology Ligand Pf Parasite growth inhibition assay - - 7.1 pIC50 3
pIC50 7.1 (IC50 7.4x10-8 M) [3]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Malaria Pharmacology Comments
The Plasmodium enzyme bifunctional farnesyl/geranylgeranyl diphosphate (PfFPPS/GGPPS) is an essential branchpoint enzyme in isoprenoid biosynthesis in the parasite [2]. Bisphosphonate drugs, that inhibit Human FDPS and GGPS1, demonstrate poor bioavailability and selectivity for PfFPPS/GGPPS leading to the identification and development of more selective compounds [1,3].

References

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1. Gisselberg JE, Herrera Z, Orchard LM, Llinás M, Yeh E. (2018) Specific Inhibition of the Bifunctional Farnesyl/Geranylgeranyl Diphosphate Synthase in Malaria Parasites via a New Small-Molecule Binding Site. Cell Chem Biol, 25 (2): 185-193.e5. [PMID:29276048]

2. Jordão FM, Gabriel HB, Alves JM, Angeli CB, Bifano TD, Breda A, de Azevedo MF, Basso LA, Wunderlich G, Kimura EA et al.. (2013) Cloning and characterization of bifunctional enzyme farnesyl diphosphate/geranylgeranyl diphosphate synthase from Plasmodium falciparum. Malar J, 12: 184. [PMID:23734739]

3. Kabeche S, Aida J, Akther T, Ichikawa T, Ochida A, Pulkoski-Gross MJ, Smith M, Humphries PS, Yeh E. (2021) Nonbisphosphonate inhibitors of Plasmodium falciparum FPPS/GGPPS. Bioorg Med Chem Lett, 41: 127978. [PMID:33766764]

How to cite this page

Isoprenoid biosynthesis enzymes : Plasmodium falciparum bifunctional farnesyl/geranylgeranyl diphosphate synthase. Last modified on 13/12/2021. Accessed on 21/01/2022. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=3173.