PDBsum entry 3kvx

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Transferase PDB id
Protein chain
330 a.a. *
Waters ×27
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Jnk3 bound to aminopyrimidine inhibitor, sr-3562
Structure: Mitogen-activated protein kinase 10. Chain: a. Fragment: residues 39-402. Synonym: stress-activated protein kinase jnk3, c-jun n-term kinase 3, map kinase p49 3f12. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: mapk10, jnk3, jnk3a, prkm10. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.40Å     R-factor:   0.222     R-free:   0.269
Authors: J.E.Habel,J.D.Laughlin,P.Lograsso
Key ref: T.Kamenecka et al. (2010). Synthesis, biological evaluation, X-ray structure, and pharmacokinetics of aminopyrimidine c-jun-N-terminal kinase (JNK) inhibitors. J Med Chem, 53, 419-431. PubMed id: 19947601
30-Nov-09     Release date:   22-Dec-09    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P53779  (MK10_HUMAN) -  Mitogen-activated protein kinase 10
464 a.a.
330 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - Mitogen-activated protein 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!
  Biological process     protein phosphorylation   1 term 
  Biochemical function     transferase activity, transferring phosphorus-containing groups     5 terms  


J Med Chem 53:419-431 (2010)
PubMed id: 19947601  
Synthesis, biological evaluation, X-ray structure, and pharmacokinetics of aminopyrimidine c-jun-N-terminal kinase (JNK) inhibitors.
T.Kamenecka, R.Jiang, X.Song, D.Duckett, W.Chen, Y.Y.Ling, J.Habel, J.D.Laughlin, J.Chambers, M.Figuera-Losada, M.D.Cameron, L.Lin, C.H.Ruiz, P.V.LoGrasso.
Given the significant body of data supporting an essential role for c-jun-N-terminal kinase (JNK) in neurodegenerative disorders, we set out to develop highly selective JNK inhibitors with good cell potency and good brain penetration properties. The structure-activity relationships (SAR) around a series of aminopyrimidines were evaluated utilizing biochemical and cell-based assays to measure JNK inhibition and brain penetration in mice. Microsomal stability in three species, P450 inhibition, inhibition of generation of reactive oxygen species (ROS), and pharmacokinetics in rats were also measured. Compounds 9g, 9i, 9j, and 9l had greater than 135-fold selectivity over p38, and cell-based IC(50) values < 100 nM. Moreover, compound 9l showed an IC(50) = 0.8 nM for inhibition of ROS and had good pharmacokinetic properties in rats along with a brain-to-plasma ratio of 0.75. These results suggest that biaryl substituted aminopyrimidines represented by compound 9l may serve as the first small molecule inhibitors to test efficacy of JNK inhibitors in neurodegenerative disorders.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21185177 R.Noël, Y.Shin, X.Song, Y.He, M.Koenig, W.Chen, Y.Y.Ling, L.Lin, C.H.Ruiz, P.LoGrasso, M.D.Cameron, D.R.Duckett, and T.M.Kamenecka (2011).
Synthesis and SAR of 4-(pyrazol-3-yl)-pyridines as novel c-jun N-terminal kinase inhibitors.
  Bioorg Med Chem Lett, 21, 2732-2735.  
21458276 S.K.De, E.Barile, V.Chen, J.L.Stebbins, J.F.Cellitti, T.Machleidt, C.B.Carlson, L.Yang, R.Dahl, and M.Pellecchia (2011).
Design, synthesis, and structure-activity relationship studies of thiophene-3-carboxamide derivatives as dual inhibitors of the c-Jun N-terminal kinase.
  Bioorg Med Chem, 19, 2582-2588.  
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