Biochemical and cellular characterisation of the Plasmodium falciparum M1 alanyl aminopeptidase (PfM1AAP) and M17 leucyl aminopeptidase (PfM17LAP).
Animals
Antimalarials
/ pharmacology
CD13 Antigens
/ antagonists & inhibitors
Cell Fractionation
Cells, Cultured
Cytosol
/ enzymology
Drug Development
Enzyme Assays
Erythrocytes
/ parasitology
Humans
Hydrogen-Ion Concentration
Leucyl Aminopeptidase
/ antagonists & inhibitors
Malaria, Falciparum
/ drug therapy
Plasmodium falciparum
/ drug effects
Protozoan Proteins
/ antagonists & inhibitors
Rabbits
Recombinant Proteins
/ chemistry
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
03 02 2021
03 02 2021
Historique:
received:
25
06
2020
accepted:
18
01
2021
entrez:
4
2
2021
pubmed:
5
2
2021
medline:
16
11
2021
Statut:
epublish
Résumé
The Plasmodium falciparum M1 alanyl aminopeptidase and M17 leucyl aminopeptidase, PfM1AAP and PfM17LAP, are potential targets for novel anti-malarial drug development. Inhibitors of these aminopeptidases have been shown to kill malaria parasites in culture and reduce parasite growth in murine models. The two enzymes may function in the terminal stages of haemoglobin digestion, providing free amino acids for protein synthesis by the rapidly growing intra-erythrocytic parasites. Here we have performed a comparative cellular and biochemical characterisation of the two enzymes. Cell fractionation and immunolocalisation studies reveal that both enzymes are associated with the soluble cytosolic fraction of the parasite, with no evidence that they are present within other compartments, such as the digestive vacuole (DV). Enzyme kinetic studies show that the optimal pH of both enzymes is in the neutral range (pH 7.0-8.0), although PfM1AAP also possesses some activity (< 20%) at the lower pH range of 5.0-5.5. The data supports the proposal that PfM1AAP and PfM17LAP function in the cytoplasm of the parasite, likely in the degradation of haemoglobin-derived peptides generated in the DV and transported to the cytosol.
Identifiants
pubmed: 33536500
doi: 10.1038/s41598-021-82499-4
pii: 10.1038/s41598-021-82499-4
pmc: PMC7858622
doi:
Substances chimiques
Antimalarials
0
Protozoan Proteins
0
Recombinant Proteins
0
Leucyl Aminopeptidase
EC 3.4.11.1
CD13 Antigens
EC 3.4.11.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2854Subventions
Organisme : CIHR
Pays : Canada
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