PDBsum entry 3ezv

Go to PDB code: 
protein ligands links
Transferase PDB id
Protein chain
277 a.a. *
Waters ×143
* Residue conservation analysis
PDB id:
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
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
23-Oct-08     Release date:   03-Feb-09    
Go to PROCHECK summary

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

 Enzyme reactions 
   Enzyme class: E.C.  - Cyclin-dependent kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
+ protein
+ 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  


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.
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.  
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.