spacer
spacer

PDBsum entry 2f2c

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Cell cycle/transferase PDB id
2f2c
Jmol
Contents
Protein chains
244 a.a. *
280 a.a. *
Ligands
SO4
AP9
DMS
* Residue conservation analysis
PDB id:
2f2c
Name: Cell cycle/transferase
Title: X-ray structure of human cdk6-vcyclinwith the inhibitor aminopurvalanol
Structure: Cyclin homolog. Chain: a. Synonym: v-cyclin. Engineered: yes. Cell division protein kinase 6. Chain: b. Fragment: fragment 1-308. Synonym: serine/threonine-protein kinase plstire. Engineered: yes
Source: Herpesvirus saimiri (strain 11). Organism_taxid: 10383. Strain: 11. Gene: 72, eclf2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Homo sapiens. Human. Organism_taxid: 9606.
Biol. unit: Dimer (from PQS)
Resolution:
2.80Å     R-factor:   0.241     R-free:   0.301
Authors: U Schulze-Gahmen,H.Lu
Key ref: H.Lu and U.Schulze-Gahmen (2006). Toward understanding the structural basis of cyclin-dependent kinase 6 specific inhibition. J Med Chem, 49, 3826-3831. PubMed id: 16789739 DOI: 10.1021/jm0600388
Date:
16-Nov-05     Release date:   13-Jun-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q01043  (CGH2_SHV21) -  Cyclin homolog
Seq:
Struc:
254 a.a.
244 a.a.
Protein chain
Pfam   ArchSchema ?
Q00534  (CDK6_HUMAN) -  Cyclin-dependent kinase 6
Seq:
Struc:
326 a.a.
280 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chain B: E.C.2.7.11.22  - Cyclin-dependent kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
ATP
+ protein
= ADP
+ phosphoprotein
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cell projection   10 terms 
  Biological process     viral reproduction   37 terms 
  Biochemical function     nucleotide binding     10 terms  

 

 
    reference    
 
 
DOI no: 10.1021/jm0600388 J Med Chem 49:3826-3831 (2006)
PubMed id: 16789739  
 
 
Toward understanding the structural basis of cyclin-dependent kinase 6 specific inhibition.
H.Lu, U.Schulze-Gahmen.
 
  ABSTRACT  
 
Cyclin-dependent kinases (CDKs) are key players in cell cycle control, and genetic alterations of CDKs and their regulators have been linked to a variety of cancers. Hence, CDKs are obvious targets for therapeutic intervention in various proliferative diseases, including cancer. To date, drug design efforts have mostly focused on CDK2 because methods for crystallization of its inhibitor complexes have been well established. CDK4 and CDK6, however, may be at least as important as enzymes for cell cycle regulation and could provide alternative treatment options. We describe here two complex structures of human CDK6 with a very specific kinase inhibitor, PD0332991, which is based on a pyrido[2,3-d]pyrimidin-7-one scaffold, and with the less specific aminopurvalanol inhibitor. Analysis of the structures suggests that relatively small conformational differences between CDK2 and CDK6 in the hinge region are contributing to the inhibitor specificity by inducing changes in the inhibitor orientation that lead to sterical clashes in CDK2 but not CDK6. These complex structures provide valuable insights for the future development of CDK-specific inhibitors.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19723060 J.Wesierska-Gadek, and V.Krystof (2009).
Selective cyclin-dependent kinase inhibitors discriminating between cell cycle and transcriptional kinases: future reality or utopia?
  Ann N Y Acad Sci, 1171, 228-241.  
19296866 L.N.Johnson (2009).
Protein kinase inhibitors: contributions from structure to clinical compounds.
  Q Rev Biophys, 42, 1.  
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.