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PDBsum entry 3cg2

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protein ligands links
Transferase PDB id
3cg2
Jmol
Contents
Protein chain
327 a.a. *
Ligands
N4D
Waters ×37
* Residue conservation analysis
Superseded by: 3l8x
PDB id:
3cg2
Name: Transferase
Title: P38 alpha kinase complexed with a pyrazolo-pyrimidine based inhibitor
Structure: Mitogen-activated protein kinase 14. Chain: a. Synonym: mitogen-activated protein kinase p38 alpha, map kinase p38 alpha, cytokine suppressive anti-inflammatory drug-binding protein, csaid-binding protein, csbp, max- interacting protein 2, map kinase 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. Expression_system_cell_line: bl21 de3.
Resolution:
2.15Å     R-factor:   0.296     R-free:   0.381
Authors: J.S.Sack
Key ref: J.Das et al. (2008). Pyrazolo-pyrimidines: a novel heterocyclic scaffold for potent and selective p38 alpha inhibitors. Bioorg Med Chem Lett, 18, 2652-2657. PubMed id: 18359226 DOI: 10.1016/j.bmcl.2008.03.019
Date:
04-Mar-08     Release date:   08-Apr-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q16539  (MK14_HUMAN) -  Mitogen-activated protein kinase 14
Seq:
Struc:
360 a.a.
327 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

 

 
    reference    
 
 
DOI no: 10.1016/j.bmcl.2008.03.019 Bioorg Med Chem Lett 18:2652-2657 (2008)
PubMed id: 18359226  
 
 
Pyrazolo-pyrimidines: a novel heterocyclic scaffold for potent and selective p38 alpha inhibitors.
J.Das, R.V.Moquin, S.Pitt, R.Zhang, D.R.Shen, K.W.McIntyre, K.Gillooly, A.M.Doweyko, J.S.Sack, H.Zhang, S.E.Kiefer, K.Kish, M.McKinnon, J.C.Barrish, J.H.Dodd, G.L.Schieven, K.Leftheris.
 
  ABSTRACT  
 
The synthesis and structure-activity relationships (SAR) of p38 alpha MAP kinase inhibitors based on a pyrazolo-pyrimidine scaffold are described. These studies led to the identification of compound 2x as a potent and selective inhibitor of p38 alpha MAP kinase with excellent cellular potency toward the inhibition of TNFalpha production. Compound 2x was highly efficacious in vivo in inhibiting TNFalpha production in an acute murine model of TNFalpha production. X-ray co-crystallography of a pyrazolo-pyrimidine analog 2b bound to unphosphorylated p38 alpha is also disclosed.