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PDBsum entry 2hic
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2hic

 

 

 

 

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Contents
Protein chains
282 a.a.
269 a.a.
Theoretical model
PDB id:
2hic
Name:
Title: Recognition model for cdk7-cdk2 trans-phosphorylation
Structure: Cyclin dependent kinase 2. Chain: a. Engineered: yes. Cyclin dependent kinase 7. Chain: b. Engineered: yes
Source: Homo sapiens. Human. Expressed in: escherichia coli. Expressed in: spodoptera frugiperda.
Authors: G.Lolli,L.N.Johnson
Key ref:
G.Lolli and L.N.Johnson (2007). Recognition of Cdk2 by Cdk7. Proteins, 67, 1048-1059. PubMed id: 17373709 DOI: 10.1002/prot.21370
Date:
29-Jun-06     Release date:   10-Apr-07    
PROCHECK
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 Headers
 References

Protein chain
No UniProt id for this chain
Struc: 282 a.a.
Protein chain
No UniProt id for this chain
Struc: 269 a.a.
Key:    Secondary structure

 

 
DOI no: 10.1002/prot.21370 Proteins 67:1048-1059 (2007)
PubMed id: 17373709  
 
 
Recognition of Cdk2 by Cdk7.
G.Lolli, L.N.Johnson.
 
  ABSTRACT  
 
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.
 
  Selected figure(s)  
 
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). 		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.
 
  The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2007, 67, 1048-1059) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20139727 K.A.Merrick, and R.P.Fisher (2010).
Putting one step before the other: distinct activation pathways for Cdk1 and Cdk2 bring order to the mammalian cell cycle.
  Cell Cycle, 9, 706-714.  
19911397 M.Rogalińska, J.Z.Błoński, O.Komina, P.Góralski, J.D.Zołnierczyk, H.Piekarski, T.Robak, Z.M.Kiliańska, and J.Wesierska-Gadek (2010).
R-roscovitine (Seliciclib) affects CLL cells more strongly than combinations of fludarabine or cladribine with cyclophosphamide: Inhibition of CDK7 sensitizes leukemic cells to caspase-dependent apoptosis.
  J Cell Biochem, 109, 217-235.  
19136461 G.Lolli (2009).
Binding to DNA of the RNA-polymerase II C-terminal domain allows discrimination between Cdk7 and Cdk9 phosphorylation.
  Nucleic Acids Res, 37, 1260-1268.  
19061641 K.A.Merrick, S.Larochelle, C.Zhang, J.J.Allen, K.M.Shokat, and R.P.Fisher (2008).
Distinct activation pathways confer cyclin-binding specificity on Cdk1 and Cdk2 in human cells.
  Mol Cell, 32, 662-672.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.

 

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