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PDBsum entry 3hv3

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protein ligands links
Transferase PDB id
3hv3
Jmol
Contents
Protein chain
335 a.a. *
Ligands
R49
BOG
GOL
Waters ×124
* Residue conservation analysis
PDB id:
3hv3
Name: Transferase
Title: Human p38 map kinase in complex with rl49
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. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: mapk14, csbp, csbp1, csbp2, cspb1, mxi2. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.00Å     R-factor:   0.233     R-free:   0.300
Authors: C.Gruetter,J.R.Simard,M.Getlik,D.Rauh
Key ref: S.Klüter et al. (2010). Displacement assay for the detection of stabilizers of inactive kinase conformations. J Med Chem, 53, 357-367. PubMed id: 19928858
Date:
15-Jun-09     Release date:   17-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.
335 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 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   7 terms 
  Biological process     intracellular signal transduction   70 terms 
  Biochemical function     nucleotide binding     11 terms  

 

 
    reference    
 
 
J Med Chem 53:357-367 (2010)
PubMed id: 19928858  
 
 
Displacement assay for the detection of stabilizers of inactive kinase conformations.
S.Klüter, C.Grütter, T.Naqvi, M.Rabiller, J.R.Simard, V.Pawar, M.Getlik, D.Rauh.
 
  ABSTRACT  
 
Targeting protein kinases with small molecules outside the highly conserved ATP pocket to stabilize inactive kinase conformations is becoming a more desirable approach in kinase inhibitor research, since these molecules have advanced pharmacological properties compared to compounds exclusively targeting the ATP pocket. Traditional screening approaches for kinase inhibitors are often based on enzyme activity, but they may miss inhibitors that stabilize inactive kinase conformations by enriching the active state of the kinase. Here we present the development of a kinase binding assay employing a pyrazolourea type III inhibitor and enzyme fragment complementation (EFC) technology that is suitable to screen stabilizers of enzymatically inactive kinases. To validate this assay system, we report the binding characteristics of a series of kinase inhibitors to inactive p38alpha and JNK2. Additionally, we present protein X-ray crystallography studies to examine the binding modes of potent quinoline-based DFG-out binders in p38alpha.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20336692 M.Rabiller, M.Getlik, S.Klüter, A.Richters, S.Tückmantel, J.R.Simard, and D.Rauh (2010).
Proteus in the world of proteins: conformational changes in protein kinases.
  Arch Pharm (Weinheim), 343, 193-206.  
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