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PDBsum entry 3ekn

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protein ligands links
Transferase PDB id
3ekn
Jmol
Contents
Protein chain
297 a.a. *
Ligands
GS3
Waters ×221
* Residue conservation analysis
PDB id:
3ekn
Name: Transferase
Title: Insulin receptor kinase complexed with an inhibitor
Structure: Insulin receptor. Chain: a. Fragment: kinase domain. Synonym: ir, insulin receptor subunit alpha, insulin recept beta. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: insr. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Resolution:
2.20Å     R-factor:   0.214     R-free:   0.274
Authors: S.Chamberlain,C.Atkins,F.Deanda,M.Dumble,R.Gerding,A.Groy, S.Korenchuk,R.Kumar,H.Lei,R.Mook,G.Moorthy,A.Redman,J.Rowla L.Shewchuk
Key ref: S.D.Chamberlain et al. (2009). Optimization of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine IGF-1R tyrosine kinase inhibitors towards JNK selectivity. Bioorg Med Chem Lett, 19, 360-364. PubMed id: 19071018 DOI: 10.1016/j.bmcl.2008.11.077
Date:
19-Sep-08     Release date:   30-Dec-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P06213  (INSR_HUMAN) -  Insulin receptor
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1382 a.a.
297 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.2.7.10.1  - Receptor protein-tyrosine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
ATP
+ [protein]-L-tyrosine
= ADP
+ [protein]-L-tyrosine phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biological process     transmembrane receptor protein tyrosine kinase signaling pathway   2 terms 
  Biochemical function     transferase activity, transferring phosphorus-containing groups     5 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.bmcl.2008.11.077 Bioorg Med Chem Lett 19:360-364 (2009)
PubMed id: 19071018  
 
 
Optimization of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine IGF-1R tyrosine kinase inhibitors towards JNK selectivity.
S.D.Chamberlain, A.M.Redman, J.W.Wilson, F.Deanda, J.B.Shotwell, R.Gerding, H.Lei, B.Yang, K.L.Stevens, A.M.Hassell, L.M.Shewchuk, M.A.Leesnitzer, J.L.Smith, P.Sabbatini, C.Atkins, A.Groy, J.L.Rowand, R.Kumar, R.A.Mook, G.Moorthy, S.Patnaik.
 
  ABSTRACT  
 
The SAR of C5' functional groups with terminal basic amines at the C6 aniline of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines is reported. Examples demonstrate potent inhibition of IGF-1R with 1000-fold selectivity over JNK1 and 3 in enzymatic assays.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21276204 J.Du, L.Xi, B.Lei, H.Liu, and X.Yao (2011).
Structural Requirements of Isoquinolones as Novel Selective c-Jun N-terminal Kinase 1 Inhibitors: 2D and 3D QSAR Analyses.
  Chem Biol Drug Des, 77, 248-254.  
19591900 F.Chen, K.Beezhold, and V.Castranova (2009).
JNK1, a potential therapeutic target for hepatocellular carcinoma.
  Biochim Biophys Acta, 1796, 242-251.  
19610618 R.Li, A.Pourpak, and S.W.Morris (2009).
Inhibition of the insulin-like growth factor-1 receptor (IGF1R) tyrosine kinase as a novel cancer therapy approach.
  J Med Chem, 52, 4981-5004.  
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.