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@MISC{Schrader:873031,
author = {Schrader, Tobias Erich},
title = {{N}eutron {P}rotein {C}rystallography},
reportid = {FZJ-2020-00482},
year = {2019},
abstract = {With the advent of new instruments (e. g. Imagine at HFIR,
MANDI at SNS and BIODIFF at FRMII) neutron protein
crystallography has seen a resurrection from the past
pioneering work by Goldstein. New sample environment options
at the instruments and a growing user community have greatly
enhanced the outcome of the existing neutron diffractometers
optimized for large unit cells. Measurements at 100 K in a
nitrogen gas stream (cryostream) are now routinely possible
at neutron diffractometers. Efforts to increase the flux at
the sample position and to reduce the background at the
detector enables one to measure smaller and smaller protein
crystals down to 0.1 mm3 in volume. The neutron single
crystal diffractometer BIODIFF at the research reactor Heinz
Maier-Leibnitz (FRM II) is especially designed to collect
data from crystals with large unit cells. The main field of
its application is the structural analysis of proteins,
especially the determination of hydrogen atom positions.
BIODIFF is a joint project of the Jülich Centre for Neutron
Science (JCNS) and the FRM II. BIODIFF is designed as a
monochromatic instrument with a narrow wavelength spread of
less than 3 $\%.$ To cover a large solid angle the main
detector of BIODIFF consists of a neutron imaging plate in a
cylindrical geometry with online read-out capability. With a
radius of 200 mm and a height of 450 mm it covers a solid
angle of approximately 2π with a spatial resolution of up
to 125 µm. An optical CCD-camera pointing at the sample
position is used to quickly align the sample with respect to
the neutron beam. The main advantage of BIODIFF is the
possibility to adapt the wavelength to the size of the unit
cell of the sample crystal while operating with a clean
monochromatic beam that keeps the background level low.
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 without the need to take the crystal off
from the goniometer head. 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. 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 beta-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 beta-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 which blocks the
beta-lactamase protein efficiently such the antibiotics can
work effectively.},
month = {Feb},
date = {2019-02-27},
organization = {(Russia), 27 Feb 2019 - 27 Feb 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},
typ = {PUB:(DE-HGF)17},
url = {https://juser.fz-juelich.de/record/873031},
}