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@ARTICLE{Verma:865808,
      author       = {Verma, Neha and Dollinger, Peter and Kovacic, Filip and
                      Jaeger, Karl-Erich and Gohlke, Holger},
      title        = {{T}he {M}embrane-{I}ntegrated {S}teric {C}haperone {L}if
                      {F}acilitates {A}ctive {S}ite {O}pening of {P}seudomonas
                      aeruginosa {L}ipase {A}},
      journal      = {Journal of computational chemistry},
      volume       = {4},
      number       = {6},
      issn         = {0192-8651},
      address      = {New York, NY [u.a.]},
      publisher    = {Wiley},
      reportid     = {FZJ-2019-05106},
      pages        = {500-512},
      year         = {2020},
      abstract     = {Lipases are essential and widely used biocatalysts. Hence,
                      the production of lipases requires a detailed understanding
                      of the molecular mechanism of its folding and secretion.
                      Lipase A from Pseudomonas aeruginosa, PaLipA, constitutes a
                      prominent example that has additional relevance because of
                      its role as a virulence factor in many diseases. PaLipA
                      requires the assistance of a membrane‐integrated steric
                      chaperone, the lipase‐specific foldase Lif, to achieve its
                      enzymatically active state. However, the molecular mechanism
                      of how Lif activates its cognate lipase has remained
                      elusive. Here, we show by molecular dynamics simulations at
                      the atomistic level and potential of mean force computations
                      that Lif catalyzes the activation process of PaLipA by
                      structurally stabilizing an intermediate PaLipA
                      conformation, particularly a β‐sheet in the region of
                      residues 17–30, such that the opening of PaLipA's lid
                      domain is facilitated. This opening allows substrate access
                      to PaLipA's catalytic site. A surprising and so far not
                      fully understood aspect of our study is that the open state
                      of PaLipA is unstable compared to the closed one according
                      to our computational and in vitro biochemical results. We
                      thus speculate that further interactions of PaLipA with the
                      Xcp secretion machinery and/or components of the
                      extracellular matrix contribute to the remaining activity of
                      secreted PaLipA.},
      cin          = {NIC / JSC / ICS-6 / IMET},
      ddc          = {540},
      cid          = {I:(DE-Juel1)NIC-20090406 / I:(DE-Juel1)JSC-20090406 /
                      I:(DE-Juel1)ICS-6-20110106 / I:(DE-Juel1)IMET-20090612},
      pnm          = {511 - Computational Science and Mathematical Methods
                      (POF3-511) / Forschergruppe Gohlke $(hkf7_20170501)$ /
                      Analysis of the conformational changes during activation of
                      lipase A by its foldase $(hdd16_20171101)$ / Conformational
                      dynamics of the unbound lipase-specific foldase Lif
                      $(hdd16_20161101)$},
      pid          = {G:(DE-HGF)POF3-511 / $G:(DE-Juel1)hkf7_20170501$ /
                      $G:(DE-Juel1)hdd16_20171101$ / $G:(DE-Juel1)hdd16_20161101$},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31618459},
      UT           = {WOS:000490396800001},
      doi          = {10.1002/jcc.26085},
      url          = {https://juser.fz-juelich.de/record/865808},
}