PDBsum entry 2okr

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protein Protein-protein interface(s) links
Transferase PDB id
Protein chains
339 a.a. *
24 a.a. *
Waters ×197
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of the p38a-mapkap kinase 2 heterodimer
Structure: Mitogen-activated protein kinase 14. Chain: a, d. Synonym: mitogen-activated protein kinase p38 alpha, map kinase p38 alpha, cytokine suppressive anti-inflammatory drug-binding protein, csaid-binding protein, csbp, max- interacting protein 2, map kinase mxi2, sapk2a. Engineered: yes. Map kinase-activated protein kinase 2. Chain: c, f.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: mapk14, csbp, csbp1, csbp2, mxi2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Synthetic: yes. Other_details: this sequence occurs naturally in homo sapiens (humans)
2.00Å     R-factor:   0.239     R-free:   0.272
Authors: E.Ter Haar
Key ref:
E.ter Haar et al. (2007). Crystal structure of the p38 alpha-MAPKAP kinase 2 heterodimer. J Biol Chem, 282, 9733-9739. PubMed id: 17255097 DOI: 10.1074/jbc.M611165200
17-Jan-07     Release date:   06-Feb-07    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q16539  (MK14_HUMAN) -  Mitogen-activated protein kinase 14
360 a.a.
339 a.a.
Protein chains
Pfam   ArchSchema ?
P49137  (MAPK2_HUMAN) -  MAP kinase-activated protein kinase 2
400 a.a.
24 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: Chains A, D: E.C.  - Mitogen-activated protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
+ protein
+ phosphoprotein
   Enzyme class 2: Chains C, F: E.C.  - Non-specific serine/threonine protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
+ protein
+ phosphoprotein
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
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   70 terms 
  Biochemical function     nucleotide binding     11 terms  


DOI no: 10.1074/jbc.M611165200 J Biol Chem 282:9733-9739 (2007)
PubMed id: 17255097  
Crystal structure of the p38 alpha-MAPKAP kinase 2 heterodimer.
E.ter Haar, P.Prabakhar, X.Liu, C.Lepre.
The p38 signaling pathway is activated in response to cell stress and induces production of proinflammatory cytokines. P38alpha is phosphorylated and activated in response to cell stress by MKK3 and MKK6 and in turn phosphorylates a number of substrates, including MAPKAP kinase 2 (MK2). We have determined the crystal structure of the unphosphorylated p38alpha-MK2 heterodimer. The C-terminal regulatory domain of MK2 binds in the docking groove of p38alpha, and the ATP-binding sites of both kinases are at the heterodimer interface. The conformation suggests an extra mechanism in addition to the regulation of the p38alpha and MK2 phosphorylation states that prevents phosphorylation of substrates in the absence of cell stress. Addition of constitutively active MKK6-DD results in rapid phosphorylation of the p38alpha-MK2 heterodimer.
  Selected figure(s)  
Figure 1.
FIGURE 1. Crystal structure of the p38 -MK2 heterodimer. A, side view of the p38 -MK2 heterodimer. P38 (yellow) and MK2 (magenta) are positioned "face to face" in the heterodimer, which means that the ATP-binding sites and the substrate binding grooves are at the interface of the heterodimer. The K-helix of the MK2 C-terminal regulatory domain (blue) is sandwiched between the p38 and MK2 kinase domains, whereas residues 370–393 of the C-terminal regulatory domain bind p38 in the docking groove. B, heterodimer rotated 180°. C, top view of the heterodimer.
Figure 3.
FIGURE 3. Binding of MK2 C-terminal regulatory domain in the p38 docking groove. The MK2 C-terminal regulatory domain binds both the common docking site (A) and the ED site (B). The side chains of Ala^378, Ser^379, Leu^384, and Lys^388 of MK2 have been omitted for clarity. The side chains of p38 are colored yellow. MK2 is colored purple.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2007, 282, 9733-9739) copyright 2007.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20640477 S.Kostenko, M.T.Khan, I.Sylte, and U.Moens (2011).
The diterpenoid alkaloid noroxoaconitine is a Mapkap kinase 5 (MK5/PRAK) inhibitor.
  Cell Mol Life Sci, 68, 289-301.  
20626350 A.Cuadrado, and A.R.Nebreda (2010).
Mechanisms and functions of p38 MAPK signalling.
  Biochem J, 429, 403-417.  
20932473 H.C.Reinhardt, P.Hasskamp, I.Schmedding, S.Morandell, M.A.van Vugt, X.Wang, R.Linding, S.E.Ong, D.Weaver, S.A.Carr, and M.B.Yaffe (2010).
DNA damage activates a spatially distinct late cytoplasmic cell-cycle checkpoint network controlled by MK2-mediated RNA stabilization.
  Mol Cell, 40, 34-49.  
  19937655 R.Cheng, B.Felicetti, S.Palan, I.Toogood-Johnson, C.Scheich, J.Barker, M.Whittaker, and T.Hesterkamp (2010).
High-resolution crystal structure of human Mapkap kinase 3 in complex with a high affinity ligand.
  Protein Sci, 19, 168-173.
PDB code: 3fhr
19230643 H.C.Reinhardt, and M.B.Yaffe (2009).
Kinases that control the cell cycle in response to DNA damage: Chk1, Chk2, and MK2.
  Curr Opin Cell Biol, 21, 245-255.  
19296855 M.A.Argiriadi, S.Sousa, D.Banach, D.Marcotte, T.Xiang, M.J.Tomlinson, M.Demers, C.Harris, S.Kwak, J.Hardman, M.Pietras, L.Quinn, J.DiMauro, B.Ni, J.Mankovich, D.W.Borhani, R.V.Talanian, and R.Sadhukhan (2009).
Rational mutagenesis to support structure-based drug design: MAPKAP kinase 2 as a case study.
  BMC Struct Biol, 9, 16.  
19622861 S.B.Patel, P.M.Cameron, S.J.O'Keefe, B.Frantz-Wattley, J.Thompson, E.A.O'Neill, T.Tennis, L.Liu, J.W.Becker, and G.Scapin (2009).
The three-dimensional structure of MAP kinase p38beta: different features of the ATP-binding site in p38beta compared with p38alpha.
  Acta Crystallogr D Biol Crystallogr, 65, 777-785.
PDB codes: 3gc7 3gc8 3gc9
19561096 T.Yoshizawa, D.Hammaker, D.L.Boyle, M.Corr, R.Flavell, R.Davis, G.Schett, and G.S.Firestein (2009).
Role of MAPK kinase 6 in arthritis: distinct mechanism of action in inflammation and cytokine expression.
  J Immunol, 183, 1360-1367.  
18501927 K.M.Sours, S.C.Kwok, T.Rachidi, T.Lee, A.Ring, A.N.Hoofnagle, K.A.Resing, and N.G.Ahn (2008).
Hydrogen-exchange mass spectrometry reveals activation-induced changes in the conformational mobility of p38alpha MAP kinase.
  J Mol Biol, 379, 1075-1093.  
18620516 S.Duraisamy, M.Bajpai, U.Bughani, S.G.Dastidar, A.Ray, and P.Chopra (2008).
MK2: a novel molecular target for anti-inflammatory therapy.
  Expert Opin Ther Targets, 12, 921-936.  
17765316 J.E.Clark, N.Sarafraz, and M.S.Marber (2007).
Potential of p38-MAPK inhibitors in the treatment of ischaemic heart disease.
  Pharmacol Ther, 116, 192-206.  
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 code is shown on the right.