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PDBsum entry 1oz1

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protein ligands links
Transferase PDB id
1oz1
Jmol
Contents
Protein chain
344 a.a. *
Ligands
FPH
Waters ×201
* Residue conservation analysis
PDB id:
1oz1
Name: Transferase
Title: P38 mitogen-activated kinase in complex with 4-azaindole inhibitor
Structure: Mitogen-activated protein kinase 14. Chain: a. Synonym: mitogen-activated protein kinase p38alpha, map kinase p38alpha, 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 or csbp1 or csbp2 or csbp or mxi2. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.10Å     R-factor:   0.204     R-free:   0.251
Authors: B.Lovejoy,A.Villasenor,M.Browner,P.Dunten
Key ref: A.Trejo et al. (2003). Design and synthesis of 4-azaindoles as inhibitors of p38 MAP kinase. J Med Chem, 46, 4702-4713. PubMed id: 14561090 DOI: 10.1021/jm0301787
Date:
07-Apr-03     Release date:   23-Sep-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q16539  (MK14_HUMAN) -  Mitogen-activated protein kinase 14
Seq:
Struc:
360 a.a.
344 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    
 
 
DOI no: 10.1021/jm0301787 J Med Chem 46:4702-4713 (2003)
PubMed id: 14561090  
 
 
Design and synthesis of 4-azaindoles as inhibitors of p38 MAP kinase.
A.Trejo, H.Arzeno, M.Browner, S.Chanda, S.Cheng, D.D.Comer, S.A.Dalrymple, P.Dunten, J.Lafargue, B.Lovejoy, J.Freire-Moar, J.Lim, J.Mcintosh, J.Miller, E.Papp, D.Reuter, R.Roberts, F.Sanpablo, J.Saunders, K.Song, A.Villasenor, S.D.Warren, M.Welch, P.Weller, P.E.Whiteley, L.Zeng, D.M.Goldstein.
 
  ABSTRACT  
 
Inhibition of the biosynthesis of proinflammatory cytokines such as tumor necrosis factor and interleukin-1 via p38 has been an approach toward the development of a disease modifying agent for the treatment of chronic inflammation and autoimmune diseases. The development of a new core structure of p38 inhibitors, 3-(4-fluorophenyl)-2-(pyridin-4-yl)-1H-pyrrolo[3,2-b] pyridine, is described. X-ray crystallographic data of the lead bound to the active site of p38 was used to guide the optimization of the series. Specific focus was placed on modulating the physical properties of the core while maintaining potent inhibition of p38. These efforts identified 42c as a potent inhibitor of p38, which also possessed the required physical properties worthy of advanced studies.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21515047 M.Soth, S.Abbot, A.Abubakari, N.Arora, H.Arzeno, R.Billedeau, N.Dewdney, K.Durkin, S.Frauchiger, M.Ghate, D.M.Goldstein, R.J.Hill, A.Kuglstatter, F.Li, B.Loe, K.McCaleb, J.McIntosh, E.Papp, J.Park, M.Stahl, M.L.Sung, R.Suttman, D.C.Swinney, P.Weller, B.Wong, H.Zecic, and T.Gabriel (2011).
3-Amino-pyrazolo[3,4-d]pyrimidines as p38α kinase inhibitors: Design and development to a highly selective lead.
  Bioorg Med Chem Lett, 21, 3452-3456.  
20445232 A.G.Villaseñor, A.Wong, A.Shao, A.Garg, A.Kuglstatter, and S.F.Harris (2010).
Acoustic matrix microseeding: improving protein crystal growth with minimal chemical bias.
  Acta Crystallogr D Biol Crystallogr, 66, 568-576.  
19532996 I.Kim, and J.Choi (2009).
A versatile approach to oligostilbenoid natural products--synthesis of permethylated analogues of viniferifuran, malibatol A, and shoreaphenol.
  Org Biomol Chem, 7, 2788-2795.  
20160879 R.S.Armen, J.Chen, and C.L.Brooks (2009).
An Evaluation of Explicit Receptor Flexibility in Molecular Docking Using Molecular Dynamics and Torsion Angle Molecular Dynamics.
  J Chem Theory Comput, 5, 2909-2923.  
18481343 D.Heckmann, A.Meyer, B.Laufer, G.Zahn, R.Stragies, and H.Kessler (2008).
Rational design of highly active and selective ligands for the alpha5beta1 integrin receptor.
  Chembiochem, 9, 1397-1407.  
18566506 J.S.Sack, K.F.Kish, M.Pokross, D.Xie, G.J.Duke, J.A.Tredup, S.E.Kiefer, and J.A.Newitt (2008).
Structural basis for the high-affinity binding of pyrrolotriazine inhibitors of p38 MAP kinase.
  Acta Crystallogr D Biol Crystallogr, 64, 705-710.  
17694525 D.Kuhn, N.Weskamp, E.Hüllermeier, and G.Klebe (2007).
Functional Classification of Protein Kinase Binding Sites Using Cavbase.
  ChemMedChem, 2, 1432-1447.  
16283677 G.Wagner, and S.Laufer (2006).
Small molecular anti-cytokine agents.
  Med Res Rev, 26, 1.  
16784462 S.L.Dixon, A.M.Smondyrev, and S.N.Rao (2006).
PHASE: a novel approach to pharmacophore modeling and 3D database searching.
  Chem Biol Drug Des, 67, 370-372.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.