N-terminal phosphorylation regulates the activity of glycogen synthase kinase 3 from Plasmodium falciparum.
autophosphorylation
drug target
glycogen synthase kinase
malaria
small-angle scattering
Journal
The Biochemical journal
ISSN: 1470-8728
Titre abrégé: Biochem J
Pays: England
ID NLM: 2984726R
Informations de publication
Date de publication:
11 02 2022
11 02 2022
Historique:
received:
07
12
2021
revised:
09
01
2022
accepted:
12
01
2022
pubmed:
14
1
2022
medline:
16
2
2022
entrez:
13
1
2022
Statut:
ppublish
Résumé
As the decline of malaria cases stalled over the last five years, novel targets in Plasmodium falciparum are necessary for the development of new drugs. Glycogen Synthase Kinase (PfGSK3) has been identified as a potential target, since its selective inhibitors were shown to disrupt the parasitès life cycle. In the uncanonical N-terminal region of the parasite enzyme, we identified several autophosphorylation sites and probed their role in activity regulation of PfGSK3. By combining molecular modeling with experimental small-angle X-ray scattering data, we show that increased PfGSK3 activity is promoted by conformational changes in the PfGSK3 N-terminus, triggered by N-terminal phosphorylation. Our work provides novel insights into the structure and regulation of the malarial PfGSK3.
Identifiants
pubmed: 35023554
pii: 230649
doi: 10.1042/BCJ20210829
pmc: PMC8883495
doi:
Substances chimiques
Glycogen Synthase Kinase 3
EC 2.7.11.26
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
337-356Informations de copyright
© 2022 The Author(s).
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