PDBsum entry 4dli

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protein ligands links
Transferase/transferase inhibitor PDB id
Protein chain
334 a.a.
IRG ×2
Waters ×135
PDB id:
Name: Transferase/transferase inhibitor
Title: Human p38 map kinase in complex with rl87
Structure: Mitogen-activated protein kinase 14. Chain: a. Synonym: map kinase 14, mapk 14, cytokine suppressive anti- inflammatory drug-binding protein, csaid-binding protein, c kinase mxi2, max-interacting protein 2, mitogen-activated p kinase p38 alpha, map kinase p38 alpha, stress-activated pr kinase 2a, sapk2a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: mapk14, csbp, csbp1, csbp2, cspb1, mxi2, sapk2a. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.91Å     R-factor:   0.216     R-free:   0.255
Authors: C.Gruetter,M.Getlik,J.R.Simard,D.Rauh
Key ref: M.Getlik et al. (2012). Fluorophore labeled kinase detects ligands that bind within the MAPK insert of p38α kinase. PLoS One, 7, e39713. PubMed id: 22768308 DOI: 10.1371/journal.pone.0039713
06-Feb-12     Release date:   23-Jan-13    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q16539  (MK14_HUMAN) -  Mitogen-activated protein kinase 14
360 a.a.
334 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Mitogen-activated protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
+ protein
+ 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  


DOI no: 10.1371/journal.pone.0039713 PLoS One 7:e39713 (2012)
PubMed id: 22768308  
Fluorophore labeled kinase detects ligands that bind within the MAPK insert of p38α kinase.
M.Getlik, J.R.Simard, M.Termathe, C.Grütter, M.Rabiller, W.A.van Otterlo, D.Rauh.
The vast majority of small molecules known to modulate kinase activity, target the highly conserved ATP-pocket. Consequently, such ligands are often less specific and in case of inhibitors, this leads to the inhibition of multiple kinases. Thus, selective modulation of kinase function remains a major hurdle. One of the next great challenges in kinase research is the identification of ligands which bind to less conserved sites and target the non-catalytic functions of protein kinases. However, approaches that allow for the unambiguous identification of molecules that bind to these less conserved sites are few in number. We have previously reported the use of fluorescent labels in kinases (FLiK) to develop direct kinase binding assays that exclusively detect ligands which stabilize inactive (DFG-out) kinase conformations. Here, we present the successful application of the FLiK approach to develop a high-throughput binding assay capable of directly monitoring ligand binding to a remote site within the MAPK insert of p38α mitogen-activated protein kinase (MAPK). Guided by the crystal structure of an initially identified hit molecule in complex with p38α, we developed a tight binding ligand which may serve as an ideal starting point for further investigations of the biological function of the MAPK insert in regulating the p38α signaling pathway.