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PDBsum entry 3d83

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protein ligands links
Transferase PDB id
3d83
Jmol
Contents
Protein chain
349 a.a. *
Ligands
GK6
GOL
Waters ×431
* Residue conservation analysis
PDB id:
3d83
Name: Transferase
Title: Crystal structure of p38 kinase in complex with a biphenyl a inhibitor
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
Source: Homo sapiens. Organism_taxid: 9606. Gene: mapk14, csbp, csbp1, csbp2, cspb1, mxi2. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.90Å     R-factor:   0.177     R-free:   0.218
Authors: D.O.Somers
Key ref: R.M.Angell et al. (2008). Biphenyl amide p38 kinase inhibitors 4: DFG-in and DFG-out binding modes. Bioorg Med Chem Lett, 18, 4433-4437. PubMed id: 18602262 DOI: 10.1016/j.bmcl.2008.06.028
Date:
22-May-08     Release date:   22-Jul-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.
349 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 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   8 terms 
  Biological process     intracellular signal transduction   71 terms 
  Biochemical function     nucleotide binding     11 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.bmcl.2008.06.028 Bioorg Med Chem Lett 18:4433-4437 (2008)
PubMed id: 18602262  
 
 
Biphenyl amide p38 kinase inhibitors 4: DFG-in and DFG-out binding modes.
R.M.Angell, T.D.Angell, P.Bamborough, M.J.Bamford, C.W.Chung, S.G.Cockerill, S.S.Flack, K.L.Jones, D.I.Laine, T.Longstaff, S.Ludbrook, R.Pearson, K.J.Smith, P.A.Smee, D.O.Somers, A.L.Walker.
 
  ABSTRACT  
 
The biphenyl amides (BPAs) are a series of p38alpha MAP kinase inhibitors. Compounds are able to bind to the kinase in either the DFG-in or DFG-out conformation, depending on substituents. X-ray, binding, kinetic and cellular data are shown, providing the most detailed comparison to date between potent compounds from the same chemical series that bind to different p38alpha conformations. DFG-out-binding compounds could be made more potent than DFG-in-binding compounds by increasing their size. Unexpectedly, compounds that bound to the DGF-out conformation showed diminished selectivity. The kinetics of binding to the isolated enzyme and the effects of compounds on cells were largely unaffected by the kinase conformation bound.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20924370 J.B.Bruning, A.A.Parent, G.Gil, M.Zhao, J.Nowak, M.C.Pace, C.L.Smith, P.V.Afonine, P.D.Adams, J.A.Katzenellenbogen, and K.W.Nettles (2010).
Coupling of receptor conformation and ligand orientation determine graded activity.
  Nat Chem Biol, 6, 837-843.
PDB codes: 2qxs 2qzo 3os8 3os9 3osa
20189109 P.Ranjitkar, A.M.Brock, and D.J.Maly (2010).
Affinity reagents that target a specific inactive form of protein kinases.
  Chem Biol, 17, 195-206.  
20017116 R.L.Rich, and D.G.Myszka (2010).
Grading the commercial optical biosensor literature-Class of 2008: 'The Mighty Binders'.
  J Mol Recognit, 23, 1.  
19665431 L.R.Coulthard, D.E.White, D.L.Jones, M.F.McDermott, and S.A.Burchill (2009).
p38(MAPK): stress responses from molecular mechanisms to therapeutics.
  Trends Mol Med, 15, 369-379.  
18940662 A.C.Dar, M.S.Lopez, and K.M.Shokat (2008).
Small molecule recognition of c-Src via the Imatinib-binding conformation.
  Chem Biol, 15, 1015-1022.
PDB codes: 3el7 3el8
18989991 Y.A.Ivanenkov, K.V.Balakin, and S.E.Tkachenko (2008).
New approaches to the treatment of inflammatory disease : focus on small-molecule inhibitors of signal transduction pathways.
  Drugs R D, 9, 397-434.  
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. Where a reference describes a PDB structure, the PDB codes are shown on the right.