% 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{Liao:858904,
      author       = {Liao, Qinghua and Kulkarni, Yashraj and Sengupta, Ushnish
                      and Petrović, Dušan and Mulholland, Adrian J. and van der
                      Kamp, Marc W. and Strodel, Birgit and Kamerlin, Shina
                      Caroline Lynn},
      title        = {{L}oop {M}otion in {T}riosephosphate {I}somerase {I}s {N}ot
                      a {S}imple {O}pen and {S}hut {C}ase},
      journal      = {Journal of the American Chemical Society},
      volume       = {140},
      number       = {46},
      issn         = {1520-5126},
      address      = {Washington, DC},
      publisher    = {American Chemical Society},
      reportid     = {FZJ-2018-07740},
      pages        = {15889 - 15903},
      year         = {2018},
      abstract     = {Conformational changes are crucial for the catalytic action
                      of many enzymes. A prototypical and well-studied example is
                      loop opening and closure in triosephosphate isomerase (TIM),
                      which is thought to determine the rate of catalytic turnover
                      in many circumstances. Specifically, TIM loop 6 “grips”
                      the phosphodianion of the substrate and, together with a
                      change in loop 7, sets up the TIM active site for efficient
                      catalysis. Crystal structures of TIM typically show an open
                      or a closed conformation of loop 6, with the tip of the loop
                      moving ∼7 Å between conformations. Many studies have
                      interpreted this motion as a two-state, rigid-body
                      transition. Here, we use extensive molecular dynamics
                      simulations, with both conventional and enhanced sampling
                      techniques, to analyze loop motion in apo and
                      substrate-bound TIM in detail, using five crystal structures
                      of the dimeric TIM from Saccharomyces cerevisiae. We find
                      that loop 6 is highly flexible and samples multiple
                      conformational states. Empirical valence bond simulations of
                      the first reaction step show that slight displacements away
                      from the fully closed-loop conformation can be sufficient to
                      abolish most of the catalytic activity; full closure is
                      required for efficient reaction. The conformational change
                      of the loops in TIM is thus not a simple “open and shut”
                      case and is crucial for its catalytic action. Our detailed
                      analysis of loop motion in a highly efficient enzyme
                      highlights the complexity of loop conformational changes and
                      their role in biological catalysis.},
      cin          = {ICS-6},
      ddc          = {540},
      cid          = {I:(DE-Juel1)ICS-6-20110106},
      pnm          = {551 - Functional Macromolecules and Complexes (POF3-551)},
      pid          = {G:(DE-HGF)POF3-551},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30362343},
      UT           = {WOS:000451496800048},
      doi          = {10.1021/jacs.8b09378},
      url          = {https://juser.fz-juelich.de/record/858904},
}