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@INPROCEEDINGS{Schrader:972033,
      author       = {Schrader, Tobias Erich},
      title        = {{P}rotein structures and equilibrium dynamics as seen by
                      neutrons},
      reportid     = {FZJ-2023-01042},
      year         = {2022},
      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 (see Figure 1). 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. Recently, a
                      new collimation device was added in front of the detector.
                      This allows to align the apertures included in the
                      collimation with a hexapod in all necessary degrees of
                      freedom. 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 again. 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. Time permitting, the concept of contrast matching
                      between solvent and some part of the solute will be
                      explained and its use in the techniques of small angle
                      neutron scattering (SANS) and neutron reflectometry will be
                      discussed briefly.},
      month         = {Jun},
      date          = {2022-06-19},
      organization  = {(FEBS course: Biomolecules in Action
                       III), 19 Jun 2022 - 24 Jun 2022},
      subtyp        = {Invited},
      cin          = {JCNS-FRM-II / MLZ / JCNS-1 / JCNS-4},
      cid          = {I:(DE-Juel1)JCNS-FRM-II-20110218 / I:(DE-588b)4597118-3 /
                      I:(DE-Juel1)JCNS-1-20110106 / I:(DE-Juel1)JCNS-4-20201012},
      pnm          = {6G4 - Jülich Centre for Neutron Research (JCNS) (FZJ)
                      (POF4-6G4) / 632 - Materials – Quantum, Complex and
                      Functional Materials (POF4-632)},
      pid          = {G:(DE-HGF)POF4-6G4 / G:(DE-HGF)POF4-632},
      experiment   = {EXP:(DE-MLZ)BIODIFF-20140101 / EXP:(DE-MLZ)J-NSE-20140101},
      typ          = {PUB:(DE-HGF)31},
      url          = {https://juser.fz-juelich.de/record/972033},
}