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@ARTICLE{Schulte:845271,
      author       = {Schulte, Marianne and Petrović, Dušan and Neudecker,
                      Philipp and Hartmann, Rudolf and Pietruszka, Jörg and
                      Willbold, Sabine and Willbold, Dieter and Panwalkar, Vineet},
      title        = {{C}onformational {S}ampling of the {I}ntrinsically
                      {D}isordered {C}-{T}erminal {T}ail of {DERA} {I}s
                      {I}mportant for {E}nzyme {C}atalysis},
      journal      = {ACS catalysis},
      volume       = {8},
      number       = {5},
      issn         = {2155-5435},
      address      = {Washington, DC},
      publisher    = {ACS},
      reportid     = {FZJ-2018-02552},
      pages        = {3971 - 3984},
      year         = {2018},
      abstract     = {2-Deoxyribose-5-phosphate aldolase (DERA) catalyzes the
                      reversible conversion of acetaldehyde and
                      glyceraldehyde-3-phosphate into deoxyribose-5-phosphate.
                      DERA is used as a biocatalyst for the synthesis of drugs
                      such as statins and is a promising pharmaceutical target due
                      to its involvement in nucleotide catabolism. Despite
                      previous biochemical studies suggesting the catalytic
                      importance of the C-terminal tyrosine residue found in
                      several bacterial DERAs, the structural and functional basis
                      of its participation in catalysis remains elusive because
                      the electron density for the last eight to nine residues
                      (i.e., the C-terminal tail) is absent in all available
                      crystal structures. Using a combination of NMR spectroscopy
                      and molecular dynamics simulations, we conclusively show
                      that the rarely studied C-terminal tail of E. coli DERA
                      (ecDERA) is intrinsically disordered and exists in
                      equilibrium between open and catalytically relevant closed
                      states, where the C-terminal tyrosine (Y259) enters the
                      active site. Nuclear Overhauser effect distance restraints,
                      obtained due to the presence of a substantial closed state
                      population, were used to derive the solution-state structure
                      of the ecDERA closed state. Real-time NMR hydrogen/deuterium
                      exchange experiments reveal that Y259 is required for
                      efficiency of the proton abstraction step of the catalytic
                      reaction. Phosphate titration experiments show that, in
                      addition to the phosphate-binding residues located near the
                      active site, as observed in the available crystal
                      structures, ecDERA contains previously unknown auxiliary
                      phosphate-binding residues on the C-terminal tail which
                      could facilitate in orienting Y259 in an optimal position
                      for catalysis. Thus, we present significant insights into
                      the structural and mechanistic importance of the ecDERA
                      C-terminal tail and illustrate the role of conformational
                      sampling in enzyme catalysis.},
      cin          = {ICS-6 / IBG-1 / IBOC / ZEA-3 / JARA-HPC},
      ddc          = {540},
      cid          = {I:(DE-Juel1)ICS-6-20110106 / I:(DE-Juel1)IBG-1-20101118 /
                      I:(DE-Juel1)IBOC-20090406 / I:(DE-Juel1)ZEA-3-20090406 /
                      $I:(DE-82)080012_20140620$},
      pnm          = {551 - Functional Macromolecules and Complexes (POF3-551) /
                      Computational Enzyme Design $(jics69_20151101)$},
      pid          = {G:(DE-HGF)POF3-551 / $G:(DE-Juel1)jics69_20151101$},
      typ          = {PUB:(DE-HGF)16},
      UT           = {WOS:000431727300029},
      pubmed       = {pmid:30101036},
      doi          = {10.1021/acscatal.7b04408},
      url          = {https://juser.fz-juelich.de/record/845271},
}