% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Agerschou:888242,
      author       = {Agerschou, Emil Dandanell and Borgmann, Vera and
                      Wördehoff, Michael M. and Hoyer, Wolfgang},
      title        = {{I}nhibitor and substrate cooperate to inhibit amyloid
                      fibril elongation of α-synuclein},
      journal      = {Chemical science},
      volume       = {11},
      number       = {41},
      issn         = {2041-6539},
      address      = {Cambridge},
      publisher    = {RSC},
      reportid     = {FZJ-2020-04791},
      pages        = {11331 - 11337},
      year         = {2020},
      abstract     = {In amyloid fibril elongation, soluble growth substrate
                      binds to the fibril-end and converts into the fibril
                      conformation. This process is targeted by inhibitors that
                      block fibril-ends. Here, we investigated how the elongation
                      of α-synuclein (αS) fibrils, which are associated with
                      Parkinson's disease and other synucleinopathies, is
                      inhibited by αS variants with a preformed hairpin in the
                      critical N-terminal region comprising residues 36–57. The
                      inhibitory efficiency is strongly dependent on the specific
                      position of the hairpin. We find that the inhibitor and
                      substrate concentration dependencies can be analyzed with
                      models of competitive enzyme inhibition. Remarkably, the
                      growth substrate, i.e., wild-type αS, supports inhibition
                      by stabilizing the elongation-incompetent blocked state.
                      This observation allowed us to create inhibitor–substrate
                      fusions that achieved inhibition at low nanomolar
                      concentration. We conclude that inhibitor–substrate
                      cooperativity can be exploited for the design of fibril
                      growth inhibitors.},
      cin          = {IBI-7},
      ddc          = {540},
      cid          = {I:(DE-Juel1)IBI-7-20200312},
      pnm          = {553 - Physical Basis of Diseases (POF3-553) / BETACONTROL -
                      Control of amyloid formation via beta-hairpin molecular
                      recognition features (726368)},
      pid          = {G:(DE-HGF)POF3-553 / G:(EU-Grant)726368},
      typ          = {PUB:(DE-HGF)16},
      UT           = {WOS:000582936200022},
      doi          = {10.1039/D0SC04051G},
      url          = {https://juser.fz-juelich.de/record/888242},
}