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@ARTICLE{Andexer:23196,
      author       = {Andexer, J. N. and Staunig, N. and Eggert, T. and Kratky,
                      C. and Pohl, M. and Gruber, K.},
      title        = {{H}ydroxynitrile lyases with alpha/beta-hydrolase fold: two
                      enzymes with almost identical 3{D} structures but opposite
                      enantioselectivities and different reaction mechanisms},
      journal      = {ChemBioChem},
      volume       = {13},
      issn         = {1439-4227},
      address      = {Weinheim},
      publisher    = {Wiley-VCH},
      reportid     = {PreJuSER-23196},
      pages        = {1932 - 1939},
      year         = {2012},
      note         = {We acknowledge financial support from the Austrian Science
                      Foundation (FWF) through projects P17132 (to C.K.) and L148
                      (to K.G.). X-ray diffraction data were collected at the
                      EMBL/DESY beamline X13 in Hamburg, Germany and we are
                      indebted to the beamline staff for their help. For her help
                      with enzyme purification, we thank Ilona Frindi-Wosch.},
      abstract     = {Hydroxynitrile lyases (HNLs) catalyze the cleavage of
                      cyanohydrins to yield hydrocyanic acid (HCN) and the
                      respective carbonyl compound and are key enzymes in the
                      process of cyanogenesis in plants. In organic syntheses,
                      HNLs are used as biocatalysts for the formation of
                      enantiopure cyanohydrins. We determined the structure of the
                      recently identified, R-selective HNL from Arabidopsis
                      thaliana (AtHNL) at a crystallographic resolution of 2.5 Å.
                      The structure exhibits an α/β-hydrolase fold, very similar
                      to the homologous, but S-selective, HNL from Hevea
                      brasiliensis (HbHNL). The similarities also extend to the
                      active sites of these enzymes, with a Ser-His-Asp catalytic
                      triad present in all three cases. In order to elucidate the
                      mode of substrate binding and to understand the unexpected
                      opposite enantioselectivity of AtHNL, complexes of the
                      enzyme with both (R)- and (S)-mandelonitrile were modeled
                      using molecular docking simulations. Compared to the complex
                      of HbHNL with (S)-mandelonitrile, the calculations produced
                      an approximate mirror image binding mode of the substrate
                      with the phenyl rings located at very similar positions, but
                      with the cyano groups pointing in opposite directions. A
                      catalytic mechanism for AtHNL is proposed, in which His236
                      from the catalytic triad acts as a general base and the
                      emerging negative charge on the cyano group is stabilized by
                      main-chain amide groups and an α-helix dipole very similar
                      to α/β-hydrolases. This mechanistic proposal is
                      additionally supported by mutagenesis studies.},
      keywords     = {J (WoSType)},
      cin          = {IBT-2},
      ddc          = {540},
      cid          = {I:(DE-Juel1)VDB56},
      pnm          = {Biotechnologie},
      pid          = {G:(DE-Juel1)FUEK410},
      shelfmark    = {Biochemistry $\&$ Molecular Biology / Chemistry, Medicinal},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:22851196},
      pmc          = {pmc:PMC3444685},
      UT           = {WOS:000308037100014},
      doi          = {10.1002/cbic.201200239},
      url          = {https://juser.fz-juelich.de/record/23196},
}