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PDBsum entry 3nww

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protein ligands links
Transferase/transferase inhibitor PDB id
3nww
Jmol
Contents
Protein chain
339 a.a. *
Ligands
3NW
Waters ×209
* Residue conservation analysis
PDB id:
3nww
Name: Transferase/transferase inhibitor
Title: P38 alpha kinase complexed with a 2-aminothiazol-5-yl-pyrimi inhibitor
Structure: Mitogen-activated protein kinase 14. Chain: a. Synonym: map kinase 14, mapk 14, mitogen-activated protein alpha, map kinase p38 alpha, cytokine suppressive anti-infl drug-binding protein, csaid-binding protein, csbp, max-inte protein 2, map kinase mxi2, sapk2a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: csbp, csbp1, csbp2, cspb1, mapk14, mxi2. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_cell_line: bl21(de3).
Resolution:
2.09Å     R-factor:   0.214     R-free:   0.254
Authors: J.S.Sack
Key ref: S.Lin et al. (2010). Utilization of a nitrogen-sulfur nonbonding interaction in the design of new 2-aminothiazol-5-yl-pyrimidines as p38α MAP kinase inhibitors. Bioorg Med Chem Lett, 20, 5864-5868. PubMed id: 20732813
Date:
12-Jul-10     Release date:   08-Sep-10    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q16539  (MK14_HUMAN) -  Mitogen-activated protein kinase 14
Seq:
Struc:
360 a.a.
339 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 20:5864-5868 (2010)
PubMed id: 20732813  
 
 
Utilization of a nitrogen-sulfur nonbonding interaction in the design of new 2-aminothiazol-5-yl-pyrimidines as p38α MAP kinase inhibitors.
S.Lin, S.T.Wrobleski, J.Hynes, S.Pitt, R.Zhang, Y.Fan, A.M.Doweyko, K.F.Kish, J.S.Sack, M.F.Malley, S.E.Kiefer, J.A.Newitt, M.McKinnon, J.Trzaskos, J.C.Barrish, J.H.Dodd, G.L.Schieven, K.Leftheris.
 
  ABSTRACT  
 
The design, synthesis, and structure-activity relationships (SAR) of a series of 2-aminothiazol-5-yl-pyrimidines as novel p38α MAP kinase inhibitors are described. These efforts led to the identification of 41 as a potent p38α inhibitor that utilizes a unique nitrogen-sulfur intramolecular nonbonding interaction to stabilize the conformation required for binding to the p38α active site. X-ray crystallographic studies that confirm the proposed binding mode of this class of inhibitors in p38 α and provide evidence for the proposed intramolecular nitrogen-sulfur interaction are discussed.