N-terminal phosphorylation regulates the activity of glycogen synthase kinase 3 from Plasmodium falciparum.
Biochem J
; 479(3): 337-356, 2022 02 11.
Article
em En
| MEDLINE
| ID: mdl-35023554
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Plasmodium falciparum
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Transdução de Sinais
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Modelos Moleculares
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Malária Falciparum
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Quinase 3 da Glicogênio Sintase
Idioma:
En
Revista:
Biochem J
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Alemanha