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@ARTICLE{Ciepluch:860022,
      author       = {Ciepluch, Karol and Radulescu, Aurel and Hoffmann, Ingo and
                      Raba, Andreas and Allgaier, Jürgen and Richter, Dieter and
                      Biehl, Ralf},
      title        = {{I}nfluence of {PEG}ylation on {D}omain {D}ynamics of
                      {P}hosphoglycerate {K}inase: {PEG} {A}cts {L}ike {E}ntropic
                      {S}pring for the {P}rotein},
      journal      = {Bioconjugate chemistry},
      volume       = {29},
      number       = {6},
      issn         = {1520-4812},
      address      = {Columbus, Ohio},
      publisher    = {American Chemical Society},
      reportid     = {FZJ-2019-00819},
      pages        = {1950 - 1960},
      year         = {2018},
      abstract     = {Protein–polymer conjugation is a widely used technique to
                      develop protein therapeutics with improved pharmacokinetic
                      properties as prolonged half-life, higher stability, water
                      solubility, lower immunogenicity, and antigenicity.
                      Combining biochemical methods, small angle scattering
                      (SAXS/SANS), and neutron spin–echo spectroscopy, here we
                      examine the impact of PEGylation (i.e., the covalent
                      conjugation with poly(ethylene glycol) or PEG) on structure
                      and internal domain dynamics of phosphoglycerate kinase
                      (PGK) to elucidate the reason for reduced activity that is
                      connected to PEGylation. PGK is a protein with a hinge
                      motion between the two main domains that is directly related
                      to function. We find that secondary structure and ligand
                      access to the binding sites are not affected. The ligand
                      induced cleft closing is unchanged. We observe an additional
                      internal motion between covalent bonded PEG and the protein
                      compatible with Brownian motion of PGK in a harmonic
                      potential. Entropic interaction with the full PEG chain
                      leads to a force constant of about 8 pN/nm independent of
                      PEG chain length. This additional force preserves protein
                      structure and has negligible effects on the functional
                      domain dynamics of the protein. PEGylation seems to reduce
                      activity just by acting as a local crowder for the ligands.
                      The newly identified interaction mechanism might open
                      possibilities to improve rational design of
                      protein–polymer conjugates.},
      cin          = {Neutronenstreuung ; JCNS-1 / ICS-1 / JCNS-FRM-II},
      ddc          = {540},
      cid          = {I:(DE-Juel1)JCNS-1-20110106 / I:(DE-Juel1)ICS-1-20110106 /
                      I:(DE-Juel1)JCNS-FRM-II-20110218},
      pnm          = {551 - Functional Macromolecules and Complexes (POF3-551) /
                      6G4 - Jülich Centre for Neutron Research (JCNS) (POF3-623)
                      / 6215 - Soft Matter, Health and Life Sciences (POF3-621)},
      pid          = {G:(DE-HGF)POF3-551 / G:(DE-HGF)POF3-6G4 /
                      G:(DE-HGF)POF3-6215},
      experiment   = {EXP:(DE-MLZ)KWS2-20140101},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29847099},
      UT           = {WOS:000436211700019},
      doi          = {10.1021/acs.bioconjchem.8b00203},
      url          = {https://juser.fz-juelich.de/record/860022},
}