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@ARTICLE{Werner:646219,
author = {Werner, Christian and Barthel, Tatjana and Harasimowicz,
Hugo and Marminon, Christelle and Weiss, Manfred S. and
Borgne, Marc Le and Niefind, Karsten},
title = {{C}rystallographic {F}ragment {S}creening with {CK}2α’,
an {I}soform of {H}uman {P}rotein {K}inase {CK}2 {C}atalytic
{S}ubunit, and {I}ts {U}se to {O}btain a
{CK}2α’/{H}eparin {C}omplex {S}tructure},
journal = {Kinases and Phosphatases},
volume = {4},
number = {1},
issn = {2813-3757},
address = {Basel},
publisher = {MDPI},
reportid = {PUBDB-2026-00764},
pages = {1 -},
year = {2026},
abstract = {CK2α and CK2α’, two paralogous members of the human
kinome, are catalytic subunits of protein kinase CK2.
Together with the regulatory subunit CK2β, they form
heterotetrameric holoenzymes. CK2 is the subject of efforts
to develop effective and selective inhibitors. For this,
secondary binding sites remote from the canonical ATP/GTP
cavity are critical. A crystallographic fragment screening
with CK2α’ crystals and an established molecular fragment
collection was performed to identify new ligands at known or
novel sites. It resulted in fourteen CK2α’/fragment
structures. Five fragments were found at the CK2β interface
of CK2α’ and three fragments at the established αD
pocket, which exhibits subtle differences between CK2α and
CK2α’; comparative co-crystallisations with CK2α showed
that one of them binds to the αD pocket of CK2α’
exclusively. No fragments bound at the substrate-binding
region of CK2α’, but a CK2α’ structure with dp10, a
decameric section of the substrate-competitive inhibitor
heparin, and the indenoindole-type ATP-competitive inhibitor
4w was determined. A comparison with a published CK2α/dp10
structure revealed features consistent with reports about
substrate specificity differences between the isoenzymes:
dp10 binds to CK2α’ and CK2α with opposite strand
orientations, and the local conformations of the isoenzymes
in the helix αD region are significantly different.},
cin = {EMBL-User},
cid = {I:(DE-H253)EMBL-User-20120814},
pnm = {6G3 - PETRA III (DESY) (POF4-6G3)},
pid = {G:(DE-HGF)POF4-6G3},
experiment = {EXP:(DE-H253)P-P13-20150101},
typ = {PUB:(DE-HGF)16},
doi = {10.3390/kinasesphosphatases4010001},
url = {https://bib-pubdb1.desy.de/record/646219},
}