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PDBsum entry 3e3b
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References listed in PDB file
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Key reference
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Title
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Structure of human protein kinase ck2 alpha 2 with a potent indazole-Derivative inhibitor.
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Authors
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T.Nakaniwa,
T.Kinoshita,
Y.Sekiguchi,
T.Tada,
I.Nakanishi,
K.Kitaura,
Y.Suzuki,
H.Ohno,
A.Hirasawa,
G.Tsujimoto.
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Ref.
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Acta Crystallogr Sect F Struct Biol Cryst Commun, 2009,
65,
75-79.
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PubMed id
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Abstract
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Casein kinase 2 (CK2) is a serine/threonine kinase that functions as a
heterotetramer composed of two catalytic subunits (CK2alpha1 or CK2alpha2) and
two regulatory subunits (CK2beta). The two isozymes CK2alpha1 and CK2alpha2 play
distinguishable roles in healthy subjects and in patients with diseases such as
cancer, respectively. In order to develop novel CK2alpha1-selective inhibitors,
the crystal structure of human CK2alpha2 (hCK2alpha2) complexed with a potent
CK2alpha inhibitor which binds to the active site of hCK2alpha2 was determined
and compared with that of human CK2alpha1. While the two isozymes exhibited a
high similarity with regard to the active site, the largest structural
difference between the isoforms occurred in the beta4-beta5 loop responsible for
the CK2alpha-CK2beta interface. The top of the N-terminal segment interacted
with the beta4-beta5 loop via a hydrogen bond in hCK2alpha2 but not in
hCK2alpha1. Thus, the CK2alpha-CK2beta interface is a likely target candidate
for the production of selective CK2alpha1 inhibitors.
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