PDBsum entry 3lhj

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Transferase PDB id
Protein chain
341 a.a. *
Waters ×1
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of p38a mitogen-activated protein kinase in complex with a pyrazolopyridinone inhibitor.
Structure: Mitogen-activated protein kinase 14. Chain: a. Synonym: mitogen-activated protein kinase p38 alpha, map kinase p38 alpha, cytokine suppressive anti-inflammatory drug-binding protein, csaid-binding protein, csbp, max- interacting protein 2, map kinase mxi2, sapk2a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: mapk14, csbp, csbp1, csbp2, cspb1, mxi2. Expressed in: escherichia coli. Expression_system_taxid: 562
3.31Å     R-factor:   0.217     R-free:   0.289
Authors: C.Mohr,S.Jordan
Key ref: L.H.Pettus et al. (2010). Discovery and evaluation of 7-alkyl-1,5-bis-aryl-pyrazolopyridinones as highly potent, selective, and orally efficacious inhibitors of p38alpha mitogen-activated protein kinase. J Med Chem, 53, 2973-2985. PubMed id: 20218619 DOI: 10.1021/jm100095x
22-Jan-10     Release date:   14-Apr-10    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q16539  (MK14_HUMAN) -  Mitogen-activated protein kinase 14
360 a.a.
341 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 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!
  Cellular component     cell   8 terms 
  Biological process     intracellular signal transduction   71 terms 
  Biochemical function     nucleotide binding     11 terms  


DOI no: 10.1021/jm100095x J Med Chem 53:2973-2985 (2010)
PubMed id: 20218619  
Discovery and evaluation of 7-alkyl-1,5-bis-aryl-pyrazolopyridinones as highly potent, selective, and orally efficacious inhibitors of p38alpha mitogen-activated protein kinase.
L.H.Pettus, R.P.Wurz, S.Xu, B.Herberich, B.Henkle, Q.Liu, H.J.McBride, S.Mu, M.H.Plant, C.J.Saris, L.Sherman, L.M.Wong, S.Chmait, M.R.Lee, C.Mohr, F.Hsieh, A.S.Tasker.
The p38alpha mitogen-activated protein (MAP) kinase is a central signaling molecule in many proinflammatory pathways, regulating the cellular response to a multitude of external stimuli including heat, ultraviolet radiation, osmotic shock, and a variety of cytokines especially interleukin-1beta and tumor necrosis factor alpha. Thus, inhibitors of this enzyme are postulated to have significant therapeutic potential for the treatment of rheumatoid arthritis, inflammatory bowel disease, and Crohn's disease, as well as other diseases where aberrant cytokine signaling is the driver of disease. In this communication, we describe a novel class of 7-alkyl-1,5-bis-aryl-pyrazolopyridinone-based p38alpha inhibitors. In particular, compound 3f is highly potent in the enzyme and cell-based assays, selective in an Ambit kinase screen, and efficacious (ED(50) < or = 0.01 mg/kg) in the rat collagen induced arthritis (CIA) model.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21429632 H.M.Shallal, and W.A.Russu (2011).
Discovery, synthesis, and investigation of the antitumor activity of novel piperazinylpyrimidine derivatives.
  Eur J Med Chem, 46, 2043-2057.  
20957100 P.Lan, Z.J.Huang, J.R.Sun, and W.M.Chen (2010).
3D-QSAR and Molecular Docking Studies on Fused Pyrazoles as p38α Mitogen-Activated Protein Kinase Inhibitors.
  Int J Mol Sci, 11, 3357-3374.  
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