PDBsum entry 2onl

Transferase

PDB id: 2onl

Contents

Protein chains

338 a.a. *

317 a.a. *

* Residue conservation analysis

PDB id:

2onl

Name:

Transferase

Title:

Crystal structure of the p38a-mapkap kinase 2 heterodimer

Structure:

Mitogen-activated protein kinase 14. Chain: a, b. 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, d.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: mapk14, csbp, csbp1, csbp2, mxi2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Gene: mapkapk2.

Resolution:

4.00Å R-factor: 0.315 R-free: 0.331

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

Date:

24-Jan-07 Release date: 06-Feb-07

Protein chains

Q16539  (MK14_HUMAN) -  Mitogen-activated protein kinase 14 from Homo sapiens

Seq: 360 a.a.

Struc: 338 a.a.

Protein chains

P49137  (MAPK2_HUMAN) -  MAP kinase-activated protein kinase 2 from Homo sapiens

Seq: 400 a.a.

Struc: 317 a.a.

Enzyme reactions

• Enzyme class: Chains A, B: E.C.2.7.11.24 - mitogen-activated protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

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.

ABSTRACT

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.