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PDBsum entry 2hic
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References listed in PDB file
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Key reference
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Title
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Recognition of cdk2 by cdk7.
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Authors
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G.Lolli,
L.N.Johnson.
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Ref.
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Proteins, 2007,
67,
1048-1059.
[DOI no: ]
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PubMed id
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Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
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Abstract
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Cdk7, a member of the cyclin dependent protein kinase family, regulates the
activities of other Cdks through phosphorylation on their activation segment,
and hence contributes to control of the eukaryotic cell cycle. Cdk7 is itself
phosphorylated on the activation segment. Cdk7 phosphorylates Cdk1, Cdk2, Cdk4,
and Cdk6, but only Cdk1 and Cdk2 can phosphorylate Cdk7 and none of them is able
to auto-phosphorylate. The activation segments of the Cdks are very similar in
sequence. Their specificity does not appear to be dictated by the sequences
surrounding the phosphorylation sites but by structural determinants at remote
sites. Through mutagenesis studies, we have identified regions in Cdk2
responsible for its interaction with Cdk7. A model has been built that explains
the molecular basis for the specificity observed in Cdk recognition. The two
kinases are arranged in a quasi-symmetric head-to-tail arrangement in which the
N-terminal lobe from one kinase docks against the C-terminal lobe from the other
kinase, and the activation segments are within reach of the opposite catalytic
sites. Further experiments demonstrate that cyclin A hydrophobic pocket is not a
recruitment site for Cdk7.
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Figure 2.
Figure 2. Model of Cdk7 (as enzyme) and Cdk2 (as substrate).
The model was generated by imposing constraints derived from
mutagenesis studies. Cdk7 is shown in green and Cdk2 in yellow.
(A) Cdk7 activation segment in the active conformation (blue)
was modelled on active Cdk2. Cdk2 activation segment is shown in
cyan. Residues 158-162 are missing. A red dotted curve indicates
the path that Cdk2 activation segment should follow to reach
Cdk7 active site (indicate by D137 and K139 colored in white).
(B) Cdk2  D
helix (in orange) inserts in between Cdk7 lobes close to its
hinge region (in blue).
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Figure 4.
Figure 4. Predicted interactions between Cdk7 (green) and Cdk2
(yellow). (A) Cdk7-F17 faces hydrophobic residues exposed on
Cdk2 surface. Cdk2-L166 is shown in magenta. (B) Interactions of
Cdk2-K9 with Cdk7-P214, D216 and D220 and of Cdk2-Y19 and
Cdk2-K34 with Cdk7-D216. (C) Interactions between Cdk2-K89 and
Cdk7-D104, Cdk2-R297 and Cdk7-N311 and between the C-terminal
carboxylate of Cdk2 and Cdk7-S106. (D) Cdk2-K88 and R200
interact with Cdk7-E20. Cdk7-F17 is shown together with its
contacts with Cdk2-R200 and P204.
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The above figures are
reprinted
by permission from John Wiley & Sons, Inc.:
Proteins
(2007,
67,
1048-1059)
copyright 2007.
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