Preprint

PUBDB-2021-04863

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png N-terminal phosphorylation regulates the activity of Glycogen Synthase Kinase 3 from Plasmodium falciparum

Pazicky, S.CSSB*EMBL* ; Alder, A. ; Mertens, H.EMBL* ; Svergun, D.EMBL* ; Gilberger, T. ; Loew, C. (Corresponding author)Extern*CSSB*

2021

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Please use a persistent id in citations: doi:10.1101/2021.06.18.448949  doi:10.3204/PUBDB-2021-04863

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 parasite’s life cycle. Here, we show that PfGSK3 exhibits autophosphorylation, leading to an extensive phosphorylation both in vitro and in the parasite. In the uncanonical N-terminal region of the parasite enzyme, we identified several autophosphorylation sites that regulate the activity 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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Contributing Institute(s):

1. EMBL (EMBL)
2. EMBL-User (EMBL-User)
3. CSSB-EMBL (CSSB-EMBL)
4. CSSB-EMBL-CL (CSSB-EMBL-CL)
5. CSSB-BNITM-TG (CSSB-BNITM-TG)

Research Program(s):

1. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)

Experiment(s):

1. PETRA Beamline P12 (PETRA III)

Appears in the scientific report 2021

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Database coverage:
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