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@ARTICLE{Li:280468,
      author       = {Li, Jinyu and Flick, Franziska and Verheugd, Patricia and
                      Carloni, Paolo and Lüscher, Bernhard and Rossetti, Giulia},
      title        = {{I}nsight into the {M}echanism of {I}ntramolecular
                      {I}nhibition of the {C}atalytic {A}ctivity of {S}irtuin 2
                      ({SIRT}2)},
      journal      = {PLoS one},
      volume       = {10},
      number       = {9},
      issn         = {1932-6203},
      address      = {Lawrence, Kan.},
      publisher    = {PLoS},
      reportid     = {FZJ-2016-00242},
      pages        = {e0139095 -},
      year         = {2015},
      abstract     = {Sirtuin 2 (SIRT2) is a NAD+-dependent deacetylase that has
                      been associated with neurodegeneration and cancer. SIRT2 is
                      composed of a central catalytic domain, the structure of
                      which has been solved, and N- and C-terminal extensions that
                      are thought to control SIRT2 function. However structural
                      information of these N- and C-terminal regions is missing.
                      Here, we provide the first full-length molecular models of
                      SIRT2 in the absence and presence of NAD+. We also predict
                      the structural alterations associated with phosphorylation
                      of SIRT2 at S331, a modification that inhibits catalytic
                      activity. Bioinformatics tools and molecular dynamics
                      simulations, complemented by in vitro deacetylation assays,
                      provide a consistent picture based on which the C-terminal
                      region of SIRT2 is suggested to function as an
                      autoinhibitory region. This has the capacity to partially
                      occlude the NAD+ binding pocket or stabilize the NAD+ in a
                      non-productive state. Furthermore, our simulations suggest
                      that the phosphorylation at S331 causes large conformational
                      changes in the C-terminal region that enhance the
                      autoinhibitory activity, consistent with our previous
                      findings that phosphorylation of S331 by cyclin-dependent
                      kinases inhibits SIRT2 catalytic activity. The molecular
                      insight into the role of the C-terminal region in
                      controlling SIRT2 function described in this study may be
                      useful for future design of selective inhibitors targeting
                      SIRT2 for therapeutic applications.},
      cin          = {IAS-5 / JSC / INM-9},
      ddc          = {500},
      cid          = {I:(DE-Juel1)IAS-5-20120330 / I:(DE-Juel1)JSC-20090406 /
                      I:(DE-Juel1)INM-9-20140121},
      pnm          = {511 - Computational Science and Mathematical Methods
                      (POF3-511) / 571 - Connectivity and Activity (POF3-571)},
      pid          = {G:(DE-HGF)POF3-511 / G:(DE-HGF)POF3-571},
      typ          = {PUB:(DE-HGF)16},
      UT           = {WOS:000361800700166},
      pubmed       = {pmid:26407304},
      doi          = {10.1371/journal.pone.0139095},
      url          = {https://juser.fz-juelich.de/record/280468},
}