Selective Inhibition of Plasmodium falciparum ATPase 6 by Artemisinins and Identification of New Classes of Inhibitors after Expression in Yeast.
Saccharomyces cerevisiae
antimalarial agents
drug discovery
drug resistance mechanisms
drug screening
mechanisms of action
Journal
Antimicrobial agents and chemotherapy
ISSN: 1098-6596
Titre abrégé: Antimicrob Agents Chemother
Pays: United States
ID NLM: 0315061
Informations de publication
Date de publication:
17 05 2022
17 05 2022
Historique:
pubmed:
26
4
2022
medline:
20
5
2022
entrez:
25
4
2022
Statut:
ppublish
Résumé
Treatment failures with artemisinin combination therapies (ACTs) threaten global efforts to eradicate malaria. They highlight the importance of identifying drug targets and new inhibitors and of studying how existing antimalarial classes work. Here, we report the successful development of a heterologous expression-based compound-screening tool. The validated drug target Plasmodium falciparum ATPase 6 (PfATP6) and a mammalian orthologue (sarco/endoplasmic reticulum calcium ATPase 1a [SERCA1a]) were functionally expressed in Saccharomyces cerevisiae, providing a robust, sensitive, and specific screening tool. Whole-cell and
Identifiants
pubmed: 35465707
doi: 10.1128/aac.02079-21
pmc: PMC9112895
doi:
Substances chimiques
Antimalarials
0
Artemisinins
0
Calcium-Transporting ATPases
EC 7.2.2.10
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0207921Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 204809/Z/16/Z
Pays : United Kingdom
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