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Plasmodium falciparum plasmepsin V

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Target not currently curated in GtoImmuPdb

Malaria Pharmacology Ligand  Target has curated data in GtoMPdb

Target id: 3106

Nomenclature: Plasmodium falciparum plasmepsin V

Abbreviated Name: PfPMV

Family: Antimalarial targets

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Plasmodium falciparum 3D7 - 590 PMV plasmepsin V
Database Links Click here for help
ChEMBL Target CHEMBL3559649 (Pf3D7)
PlasmoDB PF3D7_1323500 (Pf3D7)
UniProtKB Q8I6Z5 (Pf3D7)
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
WEHI-842 Small molecule or natural product Ligand has a PDB structure PfNF54

Plasmodium falciparum NF54

P. falciparum strain NF54 (PfNF54) was derived from a patient who had never left the Netherlands.
PfNF54 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is sensitive to a panel of antimalarial compounds including chloroquine and pyrimethamine.
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 Parasite gametocyte assay - - 7.4 pEC50 5
⤷ pEC50 7.4 (EC50 4x10-8 M) Giemsa-stained blood film counts: no stage II-V gametocytes were observed [5]
WEHI-842 Small molecule or natural product Ligand has a PDB structure Pf3D7

Plasmodium falciparum 3D7

P. falciparum strain 3D7 (Pf3D7) was derived from isolate NF54 by limiting dilution. The complete genome of Pf3D7 has been sequenced (GenBank: LN999946.1).
Pf3D7 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is sensitive to a panel of antimalarial compounds including chloroquine and pyrimethamine.
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 - - 6.4 pEC50 4
⤷ pEC50 6.4 (EC50 4x10-7 M) [4]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Malaria Pharmacology Comments
The P. falciparum genome encodes 10 aspartic proteases, classed together as the plasmepsin family, which are involved in diverse cellular processes [3]. The P. falciparum plasmepsin V (PfPMV) enzyme processes proteins for export into the host erythrocyte and has been shown to be essential for parasite asexual blood stage development [1-2]. PfPMV has also been shown to be essential for gametocyte development, validating it as a potential target for the development of transmission-blocking drugs [5].

References

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1. Boddey JA, Hodder AN, Günther S, Gilson PR, Patsiouras H, Kapp EA, Pearce JA, de Koning-Ward TF, Simpson RJ, Crabb BS et al.. (2010) An aspartyl protease directs malaria effector proteins to the host cell. Nature, 463 (7281): 627-31. [PMID:20130643]

2. Boonyalai N, Collins CR, Hackett F, Withers-Martinez C, Blackman MJ. (2018) Essentiality of Plasmodium falciparum plasmepsin V. PLoS ONE, 13 (12): e0207621. [PMID:30517136]

3. Coombs GH, Goldberg DE, Klemba M, Berry C, Kay J, Mottram JC. (2001) Aspartic proteases of Plasmodium falciparum and other parasitic protozoa as drug targets. Trends Parasitol., 17 (11): 532-7. [PMID:11872398]

4. Hodder AN, Sleebs BE, Czabotar PE, Gazdik M, Xu Y, O'Neill MT, Lopaticki S, Nebl T, Triglia T, Smith BJ et al.. (2015) Structural basis for plasmepsin V inhibition that blocks export of malaria proteins to human erythrocytes. Nat. Struct. Mol. Biol., 22 (8): 590-6. [PMID:26214367]

5. Jennison C, Lucantoni L, O'Neill MT, McConville R, Erickson SM, Cowman AF, Sleebs BE, Avery VM, Boddey JA. (2019) Inhibition of Plasmepsin V Activity Blocks Plasmodium falciparum Gametocytogenesis and Transmission to Mosquitoes. Cell Rep, 29 (12): 3796-3806.e4. [PMID:31851913]

How to cite this page

Antimalarial targets: Plasmodium falciparum plasmepsin V. Last modified on 29/01/2020. Accessed on 22/10/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=3106.