001     472140
005     20250724175821.0
024 7 _ |a 10.1101/2021.06.18.448949
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024 7 _ |a 10.3204/PUBDB-2021-04863
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037 _ _ |a PUBDB-2021-04863
041 _ _ |a English
100 1 _ |a Pazicky, Samuel
|0 P:(DE-H253)PIP1080467
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245 _ _ |a N-terminal phosphorylation regulates the activity of Glycogen Synthase Kinase 3 from Plasmodium falciparum
260 _ _ |c 2021
336 7 _ |a Preprint
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520 _ _ |a 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.
536 _ _ |a 6G3 - PETRA III (DESY) (POF4-6G3)
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588 _ _ |a Dataset connected to CrossRef
693 _ _ |a PETRA III
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700 1 _ |a Alder, Arne
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700 1 _ |a Mertens, Haydyn
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700 1 _ |a Svergun, Dmitri
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700 1 _ |a Gilberger, Tim
|b 4
700 1 _ |a Loew, Christian
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|e Corresponding author
773 _ _ |a 10.1101/2021.06.18.448949
856 4 _ |u https://www.biorxiv.org/content/10.1101/2021.06.18.448949v1
856 4 _ |u https://bib-pubdb1.desy.de/record/472140/files/N%20terminal%20phosphorylation%20regulates%20the%20activity%20of%20Glycogen%20Synthase%20Kinase%203%201%20from%20Plasmodium%20falciparum.pdf
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856 4 _ |u https://bib-pubdb1.desy.de/record/472140/files/N%20terminal%20phosphorylation%20regulates%20the%20activity%20of%20Glycogen%20Synthase%20Kinase%203%201%20from%20Plasmodium%20falciparum.pdf?subformat=pdfa
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913 1 _ |a DE-HGF
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914 1 _ |y 2021
915 _ _ |a OpenAccess
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915 _ _ |a Creative Commons Attribution CC BY 4.0
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