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@ARTICLE{Dai:425975,
      author       = {Dai, Shaobo and Funk, Lisa-Marie and von Pappenheim, Fabian
                      Rabe and Sautner, Viktor and Paulikat, Mirko and Schröder,
                      Benjamin and Uranga, Jon and Mata, Ricardo A. and Tittmann,
                      Kai},
      title        = {{L}ow-barrier hydrogen bonds in enzyme cooperativity},
      journal      = {Nature / Physical science},
      volume       = {573},
      number       = {7775},
      issn         = {1476-4687},
      address      = {London},
      publisher    = {Macmillan28177},
      reportid     = {PUBDB-2019-03518},
      pages        = {609 - 613},
      year         = {2019},
      note         = {© Springer Nature Limited; Post referee fulltext in
                      progress; Embargo 12 months from publication},
      abstract     = {The underlying molecular mechanisms of cooperativity and
                      allosteric regulation are well understood for many proteins,
                      with haemoglobin and aspartate transcarbamoylase serving as
                      prototypical examples1,2. The binding of effectors typically
                      causes a structural transition of the protein that is
                      propagated through signalling pathways to remote sites and
                      involves marked changes on the tertiary and sometimes even
                      the quaternary level1,2,3,4,5. However, the origin of these
                      signals and the molecular mechanism of long-range signalling
                      at an atomic level remain unclear5,6,7,8. The different
                      spatial scales and timescales in signalling pathways render
                      experimental observation challenging; in particular, the
                      positions and movement of mobile protons cannot be
                      visualized by current methods of structural analysis. Here
                      we report the experimental observation of fluctuating
                      low-barrier hydrogen bonds as switching elements in
                      cooperativity pathways of multimeric enzymes. We have
                      observed these low-barrier hydrogen bonds in
                      ultra-high-resolution X-ray crystallographic structures of
                      two multimeric enzymes, and have validated their assignment
                      using computational calculations. Catalytic events at the
                      active sites switch between low-barrier hydrogen bonds and
                      ordinary hydrogen bonds in a circuit that consists of acidic
                      side chains and water molecules, transmitting a signal
                      through the collective repositioning of protons by behaving
                      as an atomistic Newton’s cradle. The resulting
                      communication synchronizes catalysis in the oligomer. Our
                      studies provide several lines of evidence and a working
                      model for not only the existence of low-barrier hydrogen
                      bonds in proteins, but also a connection to enzyme
                      cooperativity. This finding suggests new principles of drug
                      and enzyme design, in which sequences of residues can be
                      purposefully included to enable long-range communication and
                      thus the regulation of engineered biomolecules.},
      cin          = {EMBL-User},
      ddc          = {530},
      cid          = {I:(DE-H253)EMBL-User-20120814},
      pnm          = {6G3 - PETRA III (POF3-622)},
      pid          = {G:(DE-HGF)POF3-6G3},
      experiment   = {EXP:(DE-H253)P-P13-20150101 / EXP:(DE-H253)P-P14-20150101},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:31534226},
      UT           = {WOS:000488247600064},
      doi          = {10.1038/s41586-019-1581-9},
      url          = {https://bib-pubdb1.desy.de/record/425975},
}