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Plasmodium falciparum 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase

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Target id: 3064

Nomenclature: Plasmodium falciparum 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase

Abbreviated Name: PfIspD

Family: Non-mevalonate pathway enzymes

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Plasmodium falciparum 3D7 - 734 IspD 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase, putative
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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
MMV008138 Small molecule or natural product Pf Inhibition 8.1 pIC50 2
pIC50 8.1 (IC50 7x10-9 M) [2]
Description: Enzymatic activity measured using a pyrophosphate release 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
MMV008138 Small molecule or natural product PfW2 Parasite growth inhibition assay - - 7.0 pEC50 2
pEC50 7.0 (EC50 1.1x10-7 M) [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
MMV008138 Small molecule or natural product PfDd2 Parasite growth inhibition assay - - 6.6 pIC50 3
pIC50 6.6 (IC50 2.5x10-7 M) SYBR green assay [3]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Malaria Pharmacology Comments
The non-mevalonate (MEP) pathway of isoprenoid precursor biosynthesis is utilized by bacteria, plants and apicomplexan protozoa but is not present in mammals (complete pathway for P. falciparum is available at www.wikipathways.org). Enzymes of this pathway represent promising therapeutic targets for antimalarial drug development because the pathway is present in the Plasmodium parasite but not in the human host [1].
2-C-methyl-D-erythritol 4-phosphate cytidyltransferase (PfIspD) is the third enzyme in the pathway, following PfDXR.

References

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1. Imlay LS, Armstrong CM, Masters MC, Li T, Price KE, Edwards RL, Mann KM, Li LX, Stallings CL, Berry NG et al.. (2015) Plasmodium IspD (2-C-Methyl-D-erythritol 4-Phosphate Cytidyltransferase), an Essential and Druggable Antimalarial Target. ACS Infect Dis, 1 (4): 157-167. [PMID:26783558]

2. Wu W, Herrera Z, Ebert D, Baska K, Cho SH, DeRisi JL, Yeh E. (2015) A chemical rescue screen identifies a Plasmodium falciparum apicoplast inhibitor targeting MEP isoprenoid precursor biosynthesis. Antimicrob Agents Chemother, 59 (1): 356-64. [PMID:25367906]

3. Yao ZK, Krai PM, Merino EF, Simpson ME, Slebodnick C, Cassera MB, Carlier PR. (2015) Determination of the active stereoisomer of the MEP pathway-targeting antimalarial agent MMV008138, and initial structure-activity studies. Bioorg Med Chem Lett, 25 (7): 1515-9. [PMID:25754494]

How to cite this page

Non-mevalonate pathway enzymes: Plasmodium falciparum 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase. Last modified on 02/02/2021. Accessed on 15/05/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=3064.