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PDBsum entry 3p5k

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protein ligands links
Transferase/transferase inhibitor PDB id
3p5k
Jmol
Contents
Protein chain
332 a.a.
Ligands
BOG
P5K
Waters ×105
PDB id:
3p5k
Name: Transferase/transferase inhibitor
Title: P38 inhibitor-bound
Structure: Mitogen-activated protein kinase 14. Chain: a. Synonym: map kinase 14, mapk 14, crk1, mitogen-activated pr kinase p38 alpha, map kinase p38 alpha. Engineered: yes
Source: Mus musculus. Mouse. Organism_taxid: 10090. Gene: mapk14, crk1, csbp1, csbp2. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
2.09Å     R-factor:   0.214     R-free:   0.265
Authors: H.Namboodiri
Key ref: K.Moffett et al. (2011). Discovery of a novel class of non-ATP site DFG-out state p38 inhibitors utilizing computationally assisted virtual fragment-based drug design (vFBDD). Bioorg Med Chem Lett, 21, 7155-7165. PubMed id: 22014550
Date:
08-Oct-10     Release date:   02-Nov-11    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P47811  (MK14_MOUSE) -  Mitogen-activated protein kinase 14
Seq:
Struc:
360 a.a.
332 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   6 terms 
  Biological process     intracellular signal transduction   40 terms 
  Biochemical function     nucleotide binding     10 terms  

 

 
    reference    
 
 
Bioorg Med Chem Lett 21:7155-7165 (2011)
PubMed id: 22014550  
 
 
Discovery of a novel class of non-ATP site DFG-out state p38 inhibitors utilizing computationally assisted virtual fragment-based drug design (vFBDD).
K.Moffett, Z.Konteatis, D.Nguyen, R.Shetty, J.Ludington, T.Fujimoto, K.J.Lee, X.Chai, H.Namboodiri, M.Karpusas, B.Dorsey, F.Guarnieri, M.Bukhtiyarova, E.Springman, E.Michelotti.
 
  ABSTRACT  
 
Discovery of a new class of DFG-out p38α kinase inhibitors with no hinge interaction is described. A computationally assisted, virtual fragment-based drug design (vFBDD) platform was utilized to identify novel non-aromatic fragments which make productive hydrogen bond interactions with Arg 70 on the αC-helix. Molecules incorporating these fragments were found to be potent inhibitors of p38 kinase. X-ray co-crystal structures confirmed the predicted binding modes. A lead compound was identified as a potent (p38α IC(50)=22 nM) and highly selective (≥ 150-fold against 150 kinase panel) DFG-out p38 kinase inhibitor.