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PDBsum entry 2vv9

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protein ligands links
Transferase PDB id
2vv9
Jmol
Contents
Protein chain
280 a.a. *
Ligands
IM9
Waters ×152
* Residue conservation analysis
PDB id:
2vv9
Name: Transferase
Title: Cdk2 in complex with an imidazole piperazine
Structure: Cell division protein kinase 2. Chain: a. Synonym: p33 protein kinase, cyclin dependent kinase 2. Engineered: yes. Other_details: acetylation at n-terminal methionine
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf21.
Resolution:
1.90Å     R-factor:   0.191     R-free:   0.228
Authors: D.G.Acton,M.Anderson,D.M.Andrews,A.J.Barker,C.A.Brassington, M.R.Finlay,E.Fisher,S.Gerhardt,M.A.Graham,C.P.Green,D.W.Hea S.A.Loddick,R.Morgentin,J.Read,A.Roberts,J.Stanway,J.A.Tuck H.M.Weir
Key ref: M.R.Finlay et al. (2008). Imidazole piperazines: SAR and development of a potent class of cyclin-dependent kinase inhibitors with a novel binding mode. Bioorg Med Chem Lett, 18, 4442-4446. PubMed id: 18617397 DOI: 10.1016/j.bmcl.2008.06.027
Date:
04-Jun-08     Release date:   05-Aug-08    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
Seq:
Struc:
298 a.a.
279 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: 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     cyclin-dependent protein kinase holoenzyme complex   15 terms 
  Biological process     regulation of gene silencing   28 terms 
  Biochemical function     nucleotide binding     12 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.bmcl.2008.06.027 Bioorg Med Chem Lett 18:4442-4446 (2008)
PubMed id: 18617397  
 
 
Imidazole piperazines: SAR and development of a potent class of cyclin-dependent kinase inhibitors with a novel binding mode.
M.R.Finlay, D.G.Acton, D.M.Andrews, A.J.Barker, M.Dennis, E.Fisher, M.A.Graham, C.P.Green, D.W.Heaton, G.Karoutchi, S.A.Loddick, R.Morgentin, A.Roberts, J.A.Tucker, H.M.Weir.
 
  ABSTRACT  
 
A piperazine series of cyclin-dependent kinase (CDK) inhibitors have been identified. The compounds exhibit excellent physiochemical properties and a novel binding mode, whereby a bridging interaction via a water molecule with Asp 86 of CDK2, leads to selectivity for the CDK family of enzymes over other kinases. Piperazines 2e and 2i were subsequently shown to inhibit tumour growth when dosed orally in a nude mouse xenograft study. Additional chemical series that exploit this unexpected interaction with Asp 86 are also described.