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PDBsum entry 3iph

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protein ligands links
Transferase PDB id
3iph
Jmol
Contents
Protein chain
347 a.a. *
Ligands
G11
SO4
GOL ×6
Waters ×343
* Residue conservation analysis
PDB id:
3iph
Name: Transferase
Title: Crystal structure of p38 in complex with a biphenylamide inh
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: mapk14, csbp, csbp1, csbp2, cspb1, mxi2. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.10Å     R-factor:   0.184     R-free:   0.249
Authors: D.O.Somers
Key ref: N.M.Aston et al. (2009). p38alpha mitogen-activated protein kinase inhibitors: optimization of a series of biphenylamides to give a molecule suitable for clinical progression. J Med Chem, 52, 6257-6269. PubMed id: 19772287
Date:
17-Aug-09     Release date:   24-Nov-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.
347 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.2.7.11.24  - 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    
 
 
J Med Chem 52:6257-6269 (2009)
PubMed id: 19772287  
 
 
p38alpha mitogen-activated protein kinase inhibitors: optimization of a series of biphenylamides to give a molecule suitable for clinical progression.
N.M.Aston, P.Bamborough, J.B.Buckton, C.D.Edwards, D.S.Holmes, K.L.Jones, V.K.Patel, P.A.Smee, D.O.Somers, G.Vitulli, A.L.Walker.
 
  ABSTRACT  
 
p38alpha MAP kinase is a key anti-inflammatory target for rheumatoid arthritis, influencing biosynthesis of pro-inflammatory cytokines TNFalpha and IL-1beta at a translational and transcriptional level. In this paper, we describe how we have optimized a series of novel p38alpha/beta inhibitors using crystal structures of our inhibitors bound to p38alpha, classical medicinal chemistry, and modeling of virtual libraries to derive a molecule suitable for progression into clinical development.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20673774 R.E.Hubbard (2011).
Structure-based drug discovery and protein targets in the CNS.
  Neuropharmacology, 60, 7.  
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