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PDBsum entry 3ezv

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Transferase PDB id
3ezv
Jmol
Contents
Protein chain
277 a.a. *
Ligands
EZV
Waters ×143
* Residue conservation analysis
PDB id:
3ezv
Name: Transferase
Title: Cdk-2 with indazole inhibitor 9 bound at its active site
Structure: Cell division protein kinase 2. Chain: a. Synonym: p33 protein kinase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: cdk2. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
1.99Å     R-factor:   0.228     R-free:   0.244
Authors: J.R.Kiefer,J.E.Day,N.L.Caspers,K.J.Mathis,K.K.Kretzmer, R.A.Weinberg,B.A.Reitz,R.A.Stegeman,J.I.Trujillo,W.Huang, A.Thorarensen,L.Xing,A.Wrightstone,L.Christine,R.Compton, X.Li
Key ref: J.I.Trujillo et al. (2009). 2-(6-Phenyl-1H-indazol-3-yl)-1H-benzo[d]imidazoles: design and synthesis of a potent and isoform selective PKC-zeta inhibitor. Bioorg Med Chem Lett, 19, 908-911. PubMed id: 19097791 DOI: 10.1016/j.bmcl.2008.11.105
Date:
23-Oct-08     Release date:   03-Feb-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
Seq:
Struc:
298 a.a.
277 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   27 terms 
  Biochemical function     nucleotide binding     12 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.bmcl.2008.11.105 Bioorg Med Chem Lett 19:908-911 (2009)
PubMed id: 19097791  
 
 
2-(6-Phenyl-1H-indazol-3-yl)-1H-benzo[d]imidazoles: design and synthesis of a potent and isoform selective PKC-zeta inhibitor.
J.I.Trujillo, J.R.Kiefer, W.Huang, A.Thorarensen, L.Xing, N.L.Caspers, J.E.Day, K.J.Mathis, K.K.Kretzmer, B.A.Reitz, R.A.Weinberg, R.A.Stegeman, A.Wrightstone, L.Christine, R.Compton, X.Li.
 
  ABSTRACT  
 
The inhibition of PKC-zeta has been proposed to be a potential drug target for immune and inflammatory diseases. A series of 2-(6-phenyl-1H indazol-3-yl)-1H-benzo[d]imidazoles with initial high crossover to CDK-2 has been optimized to afford potent and selective inhibitors of protein kinase c-zeta (PKC-zeta). The determination of the crystal structures of key inhibitor:CDK-2 complexes informed the design and analysis of the series. The most selective and potent analog was identified by variation of the aryl substituent at the 6-position of the indazole template to give a 4-NH(2) derivative. The analog displays good selectivity over other PKC isoforms (alpha, betaII, gamma, delta, epsilon, mu, theta, eta and iota/lambda) and CDK-2, however it displays marginal selectivity against a panel of other kinases (37 profiled).
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21435888 J.F.Djung, R.J.Mears, C.A.Montalbetti, T.S.Coulter, A.Golebiowski, A.N.Carr, O.Barker, K.D.Greis, S.Zhou, E.Dolan, and G.F.Davis (2011).
The synthesis and evaluation of indolylureas as PKCĪ± inhibitors.
  Bioorg Med Chem, 19, 2742-2750.  
19668856 L.Yuan, J.S.Seo, N.S.Kang, S.Keinan, S.E.Steele, G.A.Michelotti, W.C.Wetsel, D.N.Beratan, Y.D.Gong, T.H.Lee, and J.Hong (2009).
Identification of 3-hydroxy-2-(3-hydroxyphenyl)-4H-1-benzopyran-4-ones as isoform-selective PKC-zeta inhibitors and potential therapeutics for psychostimulant abuse.
  Mol Biosyst, 5, 927-930.  
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