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PDBsum entry 1zoh
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References listed in PDB file
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Key reference
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Title
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Inspecting the structure-Activity relationship of protein kinase ck2 inhibitors derived from tetrabromo-Benzimidazole.
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Authors
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R.Battistutta,
M.Mazzorana,
S.Sarno,
Z.Kazimierczuk,
G.Zanotti,
L.A.Pinna.
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Ref.
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Chem Biol, 2005,
12,
1211-1219.
[DOI no: ]
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PubMed id
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Abstract
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CK2 is a very pleiotropic protein kinase whose high constitutive activity is
suspected to cooperate to neoplasia. Here, the crystal structure of the
complexes between CK2 and three selective tetrabromo-benzimidazole derivatives
inhibiting CK2 with Ki values between 40 and 400 nM are presented. The ligands
bind to the CK2 active site in a different way with respect to the parent
compound TBB. They enter more deeply into the cavity, establishing halogen bonds
with the backbone of Glu114 and Val116 in the hinge region. A detailed analysis
of the interactions highlights a major role of the hydrophobic effect in
establishing the rank of potency within this class of inhibitors and shows that
polar interactions are responsible for the different orientation of the
molecules in the active site.
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Figure 4.
Figure 4. K44 Interactions
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Figure 5.
Figure 5. Stereo Representation of the Main Hydrophobic
Residues Surrounding the Inhibitors in the ATP Binding Pocket
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The above figures are
reprinted
by permission from Cell Press:
Chem Biol
(2005,
12,
1211-1219)
copyright 2005.
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