A Plasmodium falciparum protein tyrosine phosphatase inhibitor identified from the ChEMBL-NTD database blocks parasite growth.
enzymatic assay
inhibition assay
phosphatase
plasmodium
post-translational modifications
Journal
FEBS open bio
ISSN: 2211-5463
Titre abrégé: FEBS Open Bio
Pays: England
ID NLM: 101580716
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
revised:
31
03
2021
received:
14
01
2021
pubmed:
3
5
2021
medline:
1
4
2022
entrez:
2
5
2021
Statut:
ppublish
Résumé
Post-translational modifications, especially reversible phosphorylation, are among the most common mechanisms that regulate protein function and biological processes in Plasmodium species. Of the Plasmodium phosphatases, phosphatase of regenerating liver (PfPRL) is secreted and is an essential phosphatase. Here, we expressed PfPRL in a heterologous expression system, and then purified and characterized its phosphatase activity. We found that Novartis_003209, a previously identified inhibitor, inhibited the PfPRL phosphatase activity of recombinant PfPRL and blocked in vitro parasite growth in a dose-dependent manner. Further, in silico docking analysis of Novartis_003209 with all four P. falciparum tyrosine phosphatases (PTP) demonstrated that Novartis_003209 is a Plasmodium PTP inhibitor. Overall, our results identify a scaffold as a potential starting point to design a PTP-specific inhibitor.
Identifiants
pubmed: 33934569
doi: 10.1002/2211-5463.13171
pmc: PMC8255846
doi:
Substances chimiques
Tyrosine
42HK56048U
Protein Tyrosine Phosphatases
EC 3.1.3.48
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1921-1929Informations de copyright
© 2021 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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