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PDBsum entry 3oef

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protein ligands links
Transferase PDB id
3oef
Jmol
Contents
Protein chain
334 a.a. *
Ligands
BOG ×2
Waters ×329
* Residue conservation analysis
PDB id:
3oef
Name: Transferase
Title: Crystal structure of y323f inactive mutant of p38alpha map k
Structure: Mitogen-activated protein kinase 14. Chain: x. 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. 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:
1.60Å     R-factor:   0.184     R-free:   0.221
Authors: O.Livnah,N.Tzarum
Key ref: N.Tzarum et al. (2011). Active mutants of the TCR-mediated p38α alternative activation site show changes in the phosphorylation lip and DEF site formation. J Mol Biol, 405, 1154-1169. PubMed id: 21146537
Date:
12-Aug-10     Release date:   12-Jan-11    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q16539  (MK14_HUMAN) -  Mitogen-activated protein kinase 14
Seq:
Struc:
360 a.a.
334 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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    
 
 
J Mol Biol 405:1154-1169 (2011)
PubMed id: 21146537  
 
 
Active mutants of the TCR-mediated p38α alternative activation site show changes in the phosphorylation lip and DEF site formation.
N.Tzarum, R.Diskin, D.Engelberg, O.Livnah.
 
  ABSTRACT  
 
The p38α mitogen-activated protein kinase is commonly activated by dual (Thr and Tyr) phosphorylation catalyzed by mitogen-activated protein kinase kinases. However, in T-cells, upon stimulation of the T-cell receptor, p38α is activated via an alternative pathway, involving its phosphorylation by zeta-chain-associated protein kinase 70 on Tyr323, distal from the phosphorylation lip. Tyr323-phosphorylated p38α is autoactivated, resulting in monophosphorylation of Thr180. The conformational changes induced by pTyr323 mediating autoactivation are not known. The lack of pTyr323 p38α for structural studies promoted the search for Tyr323 mutations that may functionally emulate its effect when phosphorylated. Via a comprehensive mutagenesis of Tyr323, we identified mutations that rendered the kinase intrinsically active and others that displayed no activity. Crystallographic studies of selected active (p38α(Y323Q), p38α(Y323T), and p38α(Y323R)) and inactive (p38α(Y323F)) mutants revealed that substantial changes in interlobe orientation, extended conformation of the activation loop, and formation of substrate docking DEF site (docking site for extracellular signal-regulated kinase FXF) interaction pocket are associated with p38α activation.