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@MISC{Schrader:873038,
      author       = {Schrader, Tobias Erich},
      title        = {{N}eutron {P}rotein {C}rystallography and equilibrium
                      dynamics},
      reportid     = {FZJ-2020-00489},
      year         = {2019},
      abstract     = {In this lecture, an introduction into the method of neutron
                      protein crystallography will be given and the differences to
                      x-ray crystallography will be highlighted: As opposed to
                      x-rays, neutrons are scattered from the nuclei and can
                      therefore locate hydrogen atoms. Therefore, typical
                      scientific questions addressed are the determination of
                      protonation states of amino acid side chains in proteins and
                      the characterization of the hydrogen bonding networks
                      between the protein active centre and an inhibitor or
                      substrate. The neutron single crystal diffractometer BIODIFF
                      will serve as an example of a neutron protein
                      crystallography beam line. It is located at the Heinz
                      Maier-Leibnitz Zentrum, MLZ, at the research reactor (FRM
                      II) in Garching, Germany. BIODIFF is a joint project of the
                      Jülich Centre for Neutron Science (JCNS) and the Technical
                      University of Munich (TUM). BIODFF is equipped with a
                      standard Oxford Cryosystem “Cryostream 700+” which
                      allows measurements in the temperature range from 90 K up to
                      500 K. A new kappa goniometer head was added recently. This
                      allows an automated tilting of the crystal in order to
                      increase the completeness of the data set when recording
                      another set of frames in the tilted geometry. Efforts to
                      increase the flux at the sample position and to reduce the
                      background at the detector have led to the ability to
                      measure smaller and smaller protein crystals down to 0.1 mm3
                      in volume. One application example is the improvement of
                      antibiotic drugs. Many bacteria secret a protein called
                      -lactamase into their environment. This protein is able
                      to hydrolyse the four membered carbon atom ring in
                      -lactam antibiotics. These antibiotics are thereby
                      destroyed and are not harmful to the bacteria any more. This
                      mechanism causes great problems in hospitals. With neutron
                      protein crystallography we were able to find a deuterium
                      atom at the amino acid side chain glutamate 166 in the
                      -lactamase protein carrying a transition state analogue.
                      This transition state analogue stops the enzymatic reaction
                      in its first acylation step. Thereby one could identify
                      glutamate 166 as the important base taking over the hydrogen
                      atom in the acylation step. Improved antibiotics should find
                      ways to bind to this side chain in order to prevent its
                      action as a base. Or, an additional drug has to be given to
                      the patients which blocks the -lactamase protein
                      efficiently such that the antibiotics can work effectively
                      agian. The technique of neutron protein crystallography uses
                      elastic neutron scattering and gives information on the
                      structure of the protein. Inelastic neutron scattering
                      reports on the equilibrium dynamics of proteins in solution.
                      In a short excursion, neutron spin echo spectroscopy, an
                      example of an inelastic, i. e. spectroscopic neutron
                      scattering technique will be introduced which allows to
                      monitor large scale protein motions on a nanosecond
                      timescale. In case of the protein Phosphoglyceratkinase, it
                      will be shown that those motions are necessary for the
                      protein to fulfill its enzymatic function.},
      month         = {Jun},
      date          = {2019-06-25},
      organization  = {FEBS Practical Course, Biomolecules in
                       Action II ,DESY, Hamburg (Germany), 25
                       Jun 2019 - 25 Jun 2019},
      subtyp        = {Invited},
      cin          = {JCNS-FRM-II / JCNS-1 / MLZ},
      cid          = {I:(DE-Juel1)JCNS-FRM-II-20110218 /
                      I:(DE-Juel1)JCNS-1-20110106 / I:(DE-588b)4597118-3},
      pnm          = {6G4 - Jülich Centre for Neutron Research (JCNS) (POF3-623)
                      / 6G15 - FRM II / MLZ (POF3-6G15) / 6215 - Soft Matter,
                      Health and Life Sciences (POF3-621)},
      pid          = {G:(DE-HGF)POF3-6G4 / G:(DE-HGF)POF3-6G15 /
                      G:(DE-HGF)POF3-6215},
      experiment   = {EXP:(DE-MLZ)BIODIFF-20140101 / EXP:(DE-MLZ)J-NSE-20140101},
      typ          = {PUB:(DE-HGF)17},
      url          = {https://juser.fz-juelich.de/record/873038},
}