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PDBsum entry 3s3i

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protein ligands links
Transferase/transferase inhibitor PDB id
3s3i
Jmol
Contents
Protein chain
349 a.a.
Ligands
CQ0
Waters ×230
PDB id:
3s3i
Name: Transferase/transferase inhibitor
Title: P38 kinase crystal structure in complex with small molecule
Structure: Mitogen-activated protein kinase 14. Chain: a. Synonym: map kinase 14, mapk 14, cytokine suppressive anti- inflammatory drug-binding protein, csaid-binding protein, c kinase mxi2, max-interacting protein 2, mitogen-activated p kinase p38 alpha, map kinase p38 alpha, sapk2a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: csbp, csbp1, csbp2, cspb1, mapk14, mxi2. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.80Å     R-factor:   0.233     R-free:   0.258
Authors: V.Segarra,J.Aiguade,R.Roca,M.Fisher,M.Lamers
Key ref: J.Aiguadé et al. (2012). Novel triazolopyridylbenzamides as potent and selective p38α inhibitors. Bioorg Med Chem Lett, 22, 3431-3436. PubMed id: 22521646
Date:
18-May-11     Release date:   04-Apr-12    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q16539  (MK14_HUMAN) -  Mitogen-activated protein kinase 14
Seq:
Struc:
360 a.a.
349 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    
 
 
Bioorg Med Chem Lett 22:3431-3436 (2012)
PubMed id: 22521646  
 
 
Novel triazolopyridylbenzamides as potent and selective p38α inhibitors.
J.Aiguadé, C.Balagué, I.Carranco, F.Caturla, M.Domínguez, P.Eastwood, C.Esteve, J.González, W.Lumeras, A.Orellana, S.Preciado, R.Roca, L.Vidal, B.Vidal.
 
  ABSTRACT  
 
A new class of p38α inhibitors based on a biaryl-triazolopyridine scaffold was investigated. X-ray crystallographic data of the initial lead compound cocrystallised with p38α was crucial in order to uncover a unique binding mode of the inhibitor to the hinge region via a pair of water molecules. Synthesis and SAR was directed towards the improvement of binding affinity, as well as ADME properties for this new class of p38α inhibitors and ultimately afforded compounds showing good in vivo efficacy.