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PDBsum entry 3hp2

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protein ligands links
Transferase PDB id
3hp2
Jmol
Contents
Protein chain
341 a.a. *
Ligands
P36
I46 ×2
Waters ×211
* Residue conservation analysis
PDB id:
3hp2
Name: Transferase
Title: Crystal structure of human p38alpha complexed with a pyridin compound
Structure: Mitogen-activated protein kinase 14. Chain: a. Synonym: mitogen-activated protein kinase p38 alpha, map ki alpha, cytokine suppressive anti-inflammatory drug-binding csaid-binding protein, csbp, max-interacting protein 2, map mxi2, sapk2a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: csbp, csbp1, csbp2, cspb1, mapk14, mxi2, thp-1. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.15Å     R-factor:   0.208     R-free:   0.252
Authors: H.-S.Shieh,J.M.Williams,R.A.Stegeman,R.G.Kurumbail
Key ref: S.R.Selness et al. (2009). Discovery of N-substituted pyridinones as potent and selective inhibitors of p38 kinase. Bioorg Med Chem Lett, 19, 5851-5856. PubMed id: 19751974 DOI: 10.1016/j.bmcl.2009.08.082
Date:
03-Jun-09     Release date:   29-Sep-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q16539  (MK14_HUMAN) -  Mitogen-activated protein kinase 14
Seq:
Struc:
360 a.a.
341 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!
  Cellular component     cell   8 terms 
  Biological process     intracellular signal transduction   71 terms 
  Biochemical function     nucleotide binding     11 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.bmcl.2009.08.082 Bioorg Med Chem Lett 19:5851-5856 (2009)
PubMed id: 19751974  
 
 
Discovery of N-substituted pyridinones as potent and selective inhibitors of p38 kinase.
S.R.Selness, R.V.Devraj, J.B.Monahan, T.L.Boehm, J.K.Walker, B.Devadas, R.C.Durley, R.Kurumbail, H.Shieh, L.Xing, M.Hepperle, P.V.Rucker, K.D.Jerome, A.G.Benson, L.D.Marrufo, H.M.Madsen, J.Hitchcock, T.J.Owen, L.Christie, M.A.Promo, B.S.Hickory, E.Alvira, W.Naing, R.Blevis-Bal.
 
  ABSTRACT  
 
The identification and evolution of a series of potent and selective p38 inhibitors is described. p38 inhibitors based on a N-benzyl pyridinone high-throughput screening hit were prepared and their SAR explored. Their design was guided by ligand bound co-crystals of p38alpha. These efforts resulted in the identification of 12r and 19 as orally active inhibitors of p38 with significant efficacy in both acute and chronic models of inflammation.