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@ARTICLE{Shibazaki:859975,
author = {Shibazaki, Chie and Arai, Shigeki and Shimizu, Rumi and
Saeki, Morihisa and Kinoshita, Takayoshi and Ostermann,
Andreas and Schrader, Tobias E. and Kurosaki, Yuzuru and
Sunami, Tomoko and Kuroki, Ryota and Adachi, Motoyasu},
title = {{H}ydration {S}tructures of the {H}uman {P}rotein {K}inase
{CK}2α {C}larified by {J}oint {N}eutron and {X}-ray
{C}rystallography},
journal = {Journal of molecular biology},
volume = {430},
number = {24},
issn = {0022-2836},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {FZJ-2019-00781},
pages = {5094 - 5104},
year = {2018},
abstract = {Casein kinase 2 (CK2) has broad phosphorylation activity
against various regulatory proteins, which are important
survival factors in eukaryotic cells. To clarify the
hydration structure and catalytic mechanism of CK2, we
determined the crystal structure of the alpha subunit of
human CK2 containing hydrogen and deuterium atoms using
joint neutron (1.9 Å resolution) and X-ray (1.1 Å
resolution) crystallography. The analysis revealed the
structure of conserved water molecules at the active site
and a long potential hydrogen bonding network originating
from the catalytic Asp156 that is well known to enhance the
nucleophilicity of the substrate OH group to the γ-phospho
group of ATP by proton elimination. His148 and Asp214
conserved in the protein kinase family are located in the
middle of the network. The water molecule forming a hydrogen
bond with Asp214 appears to be deformed. In addition,
mutational analysis of His148 in CK2 showed significant
reductions by $40\%–75\%$ in the catalytic efficiency with
similar affinity for ATP. Likewise, remarkable reductions to
less than $5\%$ were shown by corresponding mutations on
His131 in death-associated protein kinase 1, which belongs
to a group different from that of CK2. These findings shed
new light on the catalytic mechanism of protein kinases in
which the hydrogen bond network through the C-terminal
domain may assist the general base catalyst to extract a
proton with a link to the bulk solvent via intermediates of
a pair of residues.},
cin = {JCNS-FRM-II / Neutronenstreuung ; JCNS-1},
ddc = {610},
cid = {I:(DE-Juel1)JCNS-FRM-II-20110218 /
I:(DE-Juel1)JCNS-1-20110106},
pnm = {6G15 - FRM II / MLZ (POF3-6G15) / 6215 - Soft Matter,
Health and Life Sciences (POF3-621) / 6G4 - Jülich Centre
for Neutron Research (JCNS) (POF3-623)},
pid = {G:(DE-HGF)POF3-6G15 / G:(DE-HGF)POF3-6215 /
G:(DE-HGF)POF3-6G4},
experiment = {EXP:(DE-MLZ)BIODIFF-20140101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:30359582},
UT = {WOS:000454377100019},
doi = {10.1016/j.jmb.2018.09.018},
url = {https://juser.fz-juelich.de/record/859975},
}