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PDBsum entry 3uli

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protein ligands links
Transferase/transferase inhibitor PDB id
3uli
Jmol
Contents
Protein chain
286 a.a.
Ligands
1N3
Waters ×151
PDB id:
3uli
Name: Transferase/transferase inhibitor
Title: Human cyclin dependent kinase 2 (cdk2) bound to azabenzimida derivative
Structure: Cyclin-dependent kinase 2. Chain: a. Synonym: cell division protein kinase 2, p33 protein kinase engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Collection: 7108. Gene: cdk2, cdkn2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108
Resolution:
2.00Å     R-factor:   0.238     R-free:   0.302
Authors: N.A.Larsen,J.A.Tucker,T.Wang
Key ref: T.Wang et al. (2012). Discovery of azabenzimidazole derivatives as potent, selective inhibitors of TBK1/IKKε kinases. Bioorg Med Chem Lett, 22, 2063-2069. PubMed id: 22305584
Date:
10-Nov-11     Release date:   14-Aug-13    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
Seq:
Struc:
298 a.a.
286 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   14 terms 
  Biological process     regulation of gene silencing   27 terms 
  Biochemical function     nucleotide binding     12 terms  

 

 
    reference    
 
 
Bioorg Med Chem Lett 22:2063-2069 (2012)
PubMed id: 22305584  
 
 
Discovery of azabenzimidazole derivatives as potent, selective inhibitors of TBK1/IKKε kinases.
T.Wang, M.A.Block, S.Cowen, A.M.Davies, E.Devereaux, L.Gingipalli, J.Johannes, N.A.Larsen, Q.Su, J.A.Tucker, D.Whitston, J.Wu, H.J.Zhang, M.Zinda, C.Chuaqui.
 
  ABSTRACT  
 
The design, synthesis and biological evaluation of a series of azabenzimidazole derivatives as TBK1/IKKε kinase inhibitors are described. Starting from a lead compound 1a, iterative design and SAR exploitation of the scaffold led to analogues with nM enzyme potencies against TBK1/IKKε. These compounds also exhibited excellent cellular activity against TBK1. Further structure-based design to improve selectivity over CDK2 and Aurora B resulted in compounds such as 5b-e. These probe compounds will facilitate study of the complex cancer biology of TBK1 and IKKε.