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@ARTICLE{Pazicky:472140,
      author       = {Pazicky, Samuel and Alder, Arne and Mertens, Haydyn and
                      Svergun, Dmitri and Gilberger, Tim and Loew, Christian},
      title        = {{N}-terminal phosphorylation regulates the activity of
                      {G}lycogen {S}ynthase {K}inase 3 from {P}lasmodium
                      falciparum},
      reportid     = {PUBDB-2021-04863},
      year         = {2021},
      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.},
      cin          = {EMBL / EMBL-User / CSSB-EMBL / CSSB-EMBL-CL /
                      CSSB-BNITM-TG},
      cid          = {I:(DE-H253)EMBL-20120731 / I:(DE-H253)EMBL-User-20120814 /
                      I:(DE-H253)CSSB-EMBL-20141216 /
                      I:(DE-H253)CSSB-EMBL-CL-20210806 /
                      I:(DE-H253)CSSB-BNITM-TG-20210520},
      pnm          = {6G3 - PETRA III (DESY) (POF4-6G3)},
      pid          = {G:(DE-HGF)POF4-6G3},
      experiment   = {EXP:(DE-H253)P-P12-20150101},
      typ          = {PUB:(DE-HGF)25},
      doi          = {10.1101/2021.06.18.448949},
      url          = {https://bib-pubdb1.desy.de/record/472140},
}