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dc.contributor.authorMathew, Rency
dc.contributor.authorWunderlich, Juliane
dc.contributor.authorThivierge, Karine
dc.contributor.authorCwiklinski, Krystyna
dc.contributor.authorDumont, Claire
dc.contributor.authorTilley, Leann
dc.contributor.authorRohrbach, Petra
dc.contributor.authorDalton, John P.
dc.date.accessioned2021-02-16T11:42:32Z
dc.date.available2021-02-16T11:42:32Z
dc.date.issued2021-02-03
dc.identifier.citationMathew, Rency, Wunderlich, Juliane, Thivierge, Karine, Cwiklinski, Krystyna, Dumont, Claire, Tilley, Leann, Rohrbach, Petra, Dalton, John P. (2021). Biochemical and cellular characterisation of the Plasmodium falciparum M1 alanyl aminopeptidase (PfM1AAP) and M17 leucyl aminopeptidase (PfM17LAP). Scientific Reports, 11(1), 2854. doi:10.1038/s41598-021-82499-4en_IE
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/10379/16558
dc.description.abstractThe 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.en_IE
dc.description.sponsorshipJPD is a Canada Institute of Health Research (CIHR) Canada Research Chair (Tier 1) in Infectious Diseases. KC and JPD are funded by the Science Foundation Ireland (SFI, Republic of Ireland) Research Professorship Grant (17/RP/5368) awarded to JPD. This project was supported by funding obtained from the Natural Sciences and Engineering Research Council of Canada (NSERC), CIHR and Canada Foundation for Innovation (CFI). JW was supported by a doctoral research scholarship from the Fonds Québécois de la Recherche sur la Nature et les Technologies (FQRNT).en_IE
dc.formatapplication/pdfen_IE
dc.language.isoenen_IE
dc.publisherNature Researchen_IE
dc.relation.ispartofScientific Reportsen
dc.subjectBiochemistryen_IE
dc.subjectCell biologyen_IE
dc.titleBiochemical and cellular characterisation of the Plasmodium falciparum M1 alanyl aminopeptidase (Pf M1AAP) and M17 leucyl aminopeptidase (Pf M17LAP)en_IE
dc.typeArticleen_IE
dc.date.updated2021-02-15T16:04:05Z
dc.identifier.doi10.1038/s41598-021-82499-4
dc.local.publishedsourcehttps://doi.org/10.1038/s41598-021-82499-4en_IE
dc.description.peer-reviewedpeer-reviewed
dc.contributor.funderScience Foundation Irelanden_IE
dc.contributor.funderNatural Sciences and Engineering Research Council of Canadaen_IE
dc.contributor.funderCanada Foundation for Innovationen_IE
dc.contributor.funderFonds Québécois de la Recherche sur la Nature et les Technologiesen_IE
dc.internal.rssid24817292
dc.local.contactJohn Pius Dalton. Email: johnpius.dalton@nuigalway.ie
dc.local.copyrightcheckedYes
dc.local.versionPUBLISHED
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