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PDBsum entry 1j91
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structural features underlying selective inhibition of protein kinase ck2 by ATP site-Directed tetrabromo-2-Benzotriazole.
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Authors
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R.Battistutta,
E.De moliner,
S.Sarno,
G.Zanotti,
L.A.Pinna.
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Ref.
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Protein Sci, 2001,
10,
2200-2206.
[DOI no: ]
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PubMed id
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Abstract
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Two novel crystal structures of Zea mays protein kinase CK2alpha catalytic
subunit, one in complex with the specific inhibitor
4,5,6,7-tetrabromobenzotriazole (TBB) and another in the apo-form, were solved
at 2.2 A resolution. These structures were compared with those of the enzyme in
presence of ATP and GTP (the natural cosubstrates) and the inhibitor emodin.
Interaction of TBB with the active site of CK2alpha is mainly due to van der
Waals contacts, with the ligand fitting almost perfectly the cavity. One
nitrogen of the five-membered ring interacts with two charged residues, Glu 81
and Lys 68, in the depth of the cavity, through two water molecules. These are
buried in the active site and are also generally found in the structures of
CK2alpha enzyme analyzed so far, with the exception of the complex with emodin.
In the N-terminal lobe, the position of helix alphaC is particularly well
preserved in all the structures examined; the Gly-rich loop is displaced from
the intermediate position it has in the apo-form and in the presence of the
natural cosubstrates (ATP/GTP) to either an upper (with TBB) or a lower position
(with emodin). The selectivity of TBB for CK2 appears to be mainly dictated by
the reduced size of the active site which in most other protein kinases is too
large for making stable interactions with this inhibitor.
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Figure 3.
Fig. 3. (A) Two clipped views of the active site showing
the inhibitor (as cpk model) fitting the cavity are shown. The
molecular surface of the protein is represented as a white mesh.
Bromine atoms are in red, carbon atoms in green, and nitrogen
atoms in blue. (B) Position of TBB with respect to that of ATP
(cyan) and emodin (green) in the catalytic site is shown from
different points of view. Inhibitor rings lay practically in the
same plane of the purine moiety of the natural cosubstrates
(bottom).
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The above figure is
reprinted
by permission from the Protein Society:
Protein Sci
(2001,
10,
2200-2206)
copyright 2001.
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