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PDBsum entry 2zdt

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Transferase PDB id
2zdt
Jmol
Contents
Protein chain
342 a.a. *
Ligands
46C
GOL
Waters ×162
* Residue conservation analysis
PDB id:
2zdt
Name: Transferase
Title: Crystal structure of human jnk3 complexed with an isoquinolo inhibitor
Structure: Mitogen-activated protein kinase 10. Chain: a. Fragment: residues unp 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. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.00Å     R-factor:   0.216     R-free:   0.262
Authors: S.Sogabe,Y.Asano,S.Fukumoto,N.Habuka,A.Fujishima
Key ref: Y.Asano et al. (2008). Discovery, synthesis and biological evaluation of isoquinolones as novel and highly selective JNK inhibitors (2). Bioorg Med Chem, 16, 4699-4714. PubMed id: 18313930 DOI: 10.1016/j.bmc.2008.02.028
Date:
27-Nov-07     Release date:   23-Sep-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P53779  (MK10_HUMAN) -  Mitogen-activated protein kinase 10
Seq:
Struc:
464 a.a.
342 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.7.11.24  - Mitogen-activated protein 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!
  Biological process     protein phosphorylation   1 term 
  Biochemical function     transferase activity, transferring phosphorus-containing groups     5 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.bmc.2008.02.028 Bioorg Med Chem 16:4699-4714 (2008)
PubMed id: 18313930  
 
 
Discovery, synthesis and biological evaluation of isoquinolones as novel and highly selective JNK inhibitors (2).
Y.Asano, S.Kitamura, T.Ohra, F.Itoh, M.Kajino, T.Tamura, M.Kaneko, S.Ikeda, H.Igata, T.Kawamoto, S.Sogabe, S.Matsumoto, T.Tanaka, M.Yamaguchi, H.Kimura, S.Fukumoto.
 
  ABSTRACT  
 
3-Metoxycarbonyl isoquinolone derivative 1 has been identified as a potent JNK inhibitor and significantly inhibited cardiac hypertrophy in a rat pressure-overload model. Herein, a series of isoquinolones with an imidazolylmethyl or a pyrazolylmethyl group at the 2-position were designed based on X-ray crystallographic analysis of the complex between the isoquinolone compound and JNK3, as wells as the relationship between compound lipophilicity (logD) and activity in a cell-based assay. The compounds prepared showed potent JNK1 inhibitory activities in a cell-based assay. Among them the isoquinolone derivative possessing 5-[(cyclopropylamino)carbonyl]-1-methyl-1H-pyrazole (16e) exhibited significant anti-hypertrophic activity at doses of more than 1mg/kg (po) in a pressure-overload model.
 

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.  
20527726 J.Lu, X.Gong, H.Yang, and H.Fu (2010).
Concise copper-catalyzed one-pot tandem synthesis of benzimidazo[1,2-b]isoquinolin-11-one derivatives.
  Chem Commun (Camb), 46, 4172-4174.  
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