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PDBsum entry 3ej1

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protein ligands Protein-protein interface(s) links
Transferase/cell cycle PDB id
3ej1
Jmol
Contents
Protein chains
295 a.a. *
258 a.a. *
Ligands
5BP ×2
* Residue conservation analysis
PDB id:
3ej1
Name: Transferase/cell cycle
Title: Cdk2/cyclina complexed with a pyrazolopyridazine inhibitor
Structure: Cell division protein kinase 2. Chain: a, c. Synonym: p33 protein kinase. Engineered: yes. Cyclin-a2. Chain: b, d. Fragment: unp residues 113-432. Synonym: cyclin-a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: cdk2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: ccna2, ccn1, ccna. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
3.22Å     R-factor:   0.221     R-free:   0.259
Authors: K.Stevens,M.Reno,J.Alberti,D.Price,L.Kane-Carson,V.Knick,L.S A.Hassell,J.Veal,M.Peel
Key ref: K.L.Stevens et al. (2008). Synthesis and evaluation of pyrazolo[1,5-b]pyridazines as selective cyclin dependent kinase inhibitors. Bioorg Med Chem Lett, 18, 5758-5762. PubMed id: 18835709 DOI: 10.1016/j.bmcl.2008.09.069
Date:
17-Sep-08     Release date:   21-Oct-08    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
Seq:
Struc:
298 a.a.
295 a.a.
Protein chains
Pfam   ArchSchema ?
P20248  (CCNA2_HUMAN) -  Cyclin-A2
Seq:
Struc:
432 a.a.
258 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, C: 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   30 terms 
  Biochemical function     nucleotide binding     13 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.bmcl.2008.09.069 Bioorg Med Chem Lett 18:5758-5762 (2008)
PubMed id: 18835709  
 
 
Synthesis and evaluation of pyrazolo[1,5-b]pyridazines as selective cyclin dependent kinase inhibitors.
K.L.Stevens, M.J.Reno, J.B.Alberti, D.J.Price, L.S.Kane-Carson, V.B.Knick, L.M.Shewchuk, A.M.Hassell, J.M.Veal, S.T.Davis, R.J.Griffin, M.R.Peel.
 
  ABSTRACT  
 
A novel series of pyrazolo[1,5-b]pyridazines have been synthesized and identified as cyclin dependant kinase inhibitors potentially useful for the treatment of solid tumors. Modification of the hinge-binding amine or the C(2)- and C(6)-substitutions on the pyrazolopyridazine core provided potent inhibitors of CDK4 and demonstrated enzyme selectivity against VEGFR-2 and GSK3beta.