Plasmodium falciparum 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase | Antimalarial targets | IUPHAR/MMV Guide to MALARIA PHARMACOLOGY

Top ▲

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

Target id: 3064

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

Abbreviated Name: PfIspD

Family: Antimalarial targets

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Plasmodium falciparum 3D7 - 734 IspD 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase, putative
Database Links
UniProtKB

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
MMV008138 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 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 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

Show »

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

Antimalarial targets: Plasmodium falciparum 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase. Last modified on 16/08/2019. Accessed on 21/10/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=3064.