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Plasmodium falciparum plasmepsin V

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Target id: 3106

Nomenclature: Plasmodium falciparum plasmepsin V

Abbreviated Name: PfPMV

Systematic Nomenclature: Plasmodium falciparum plasmepsin V

Family: Peptidases and proteinases (Plasmodium spp.)

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
Previous and Unofficial Names Click here for help
PMV | plasmepsin V | PF13_0133
Database Links Click here for help
ChEMBL Target
PlasmoDB
UniProtKB

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
WEHI-842 Small molecule or natural product Ligand has a PDB structure Pf Inhibition 9.7 pIC50 4
pIC50 9.7 (IC50 2x10-10 M) [4]
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 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]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
WEHI-842 Small molecule or natural product Ligand has a PDB structure Pf3D7 Parasite growth inhibition assay - - 6.4 pEC50 4
pEC50 6.4 (EC50 4x10-7 M) [4]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
WEHI-842 Small molecule or natural product Ligand has a PDB structure PfNF54 Standard membrane feeding assay (SMFA) - - - - 5
Oocyst count: WEHI-842 demonstrates a dose-dependent inhibitory effect on transmission fitness [5]
Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite)
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]. P. falciparum plasmepsin V (PfPMV) is an endoplasmic reticulum (ER) localized enzyme involved in processing proteins for export into the host erythrocyte, which is key to parasite survival and immune evasion [7]. Most exported proteins contain a signal sequence for entry into the ER as well as the Plasmodium Export Element (PEXEL) motif [6,8]. PfPMV cleaves the PEXEL motif, revealing the export signal for subsequent trafficking to the host erythrocyte [1].
This enzyme is a promising target for the development of chemotherapeutic and transmission-blocking antimalarial therapies, with studies demonstrating an essential role during both the asexual blood stage [1-2,9] and gametocytogenesis [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]

6. Maier AG, Cooke BM, Cowman AF, Tilley L. (2009) Malaria parasite proteins that remodel the host erythrocyte. Nat Rev Microbiol, 7 (5): 341-54. [PMID:19369950]

7. Maier AG, Rug M, O'Neill MT, Brown M, Chakravorty S, Szestak T, Chesson J, Wu Y, Hughes K, Coppel RL et al.. (2008) Exported proteins required for virulence and rigidity of Plasmodium falciparum-infected human erythrocytes. Cell, 134 (1): 48-61. [PMID:18614010]

8. Marti M, Good RT, Rug M, Knuepfer E, Cowman AF. (2004) Targeting malaria virulence and remodeling proteins to the host erythrocyte. Science, 306 (5703): 1930-3. [PMID:15591202]

9. Russo I, Babbitt S, Muralidharan V, Butler T, Oksman A, Goldberg DE. (2010) Plasmepsin V licenses Plasmodium proteins for export into the host erythrocyte. Nature, 463 (7281): 632-6. [PMID:20130644]

How to cite this page

Peptidases and proteinases (Plasmodium spp.): Plasmodium falciparum plasmepsin V. Last modified on 23/08/2021. Accessed on 18/09/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=3106.