PDBsum entry 1kwp

Transferase

PDB id: 1kwp

Contents

Protein chain

319 a.a. *

Metals

_HG ×14

Waters ×134

* Residue conservation analysis

PDB id:

1kwp

Name:

Transferase

Title:

Crystal structure of mapkap2

Structure:

Map kinase activated protein kinase 2. Chain: a, b. Synonym: mapkap2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

Hexamer (from PQS)

Resolution:

2.80Å R-factor: 0.233 R-free: 0.245

Authors:

W.Meng,L.L.Swenson,M.J.Fitzgibbon,K.Hayakawa,E.Ter Haar,A.E.Behrens, J.R.Fulghum,J.A.Lippke

Key ref:

W.Meng et al. (2002). Structure of mitogen-activated protein kinase-activated protein (MAPKAP) kinase 2 suggests a bifunctional switch that couples kinase activation with nuclear export. J Biol Chem, 277, 37401-37405. PubMed id: 12171911 DOI: 10.1074/jbc.C200418200

Date:

30-Jan-02 Release date: 18-Sep-02

Protein chains

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

Seq: 400 a.a.

Struc: 319 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.11.1 - non-specific serine/threonine 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.C200418200

J Biol Chem 277:37401-37405 (2002)

PubMed id: 12171911

Structure of mitogen-activated protein kinase-activated protein (MAPKAP) kinase 2 suggests a bifunctional switch that couples kinase activation with nuclear export.

W.Meng, L.L.Swenson, M.J.Fitzgibbon, K.Hayakawa, E.Ter Haar, A.E.Behrens, J.R.Fulghum, J.A.Lippke.

ABSTRACT

MAPK-activated protein kinase 2 (MAPKAPK2), one of several kinases directly phosphorylated and activated by p38 MAPK, plays a central role in the inflammatory response. The activated MAPKAPK2 phosphorylates its nuclear targets CREB/ATF1, serum response factor, and E2A protein E47 and its cytoplasmic targets HSP25/27, LSP-1, 5-lipoxygenase, glycogen synthase, and tyrosine hydroxylase. The crystal structure of unphosphorylated MAPKAPK2, determined at 2.8 A resolution, includes the kinase domain and the C-terminal regulatory domain. Although the protein is inactive, the kinase domain adopts an active conformation with aspartate 366 mimicking the missing phosphorylated threonine 222 in the activation loop. The C-terminal regulatory domain forms a helix-turn-helix plus a long strand. Phosphorylation of threonine 334, which is located between the kinase domain and the C-terminal regulatory domain, may serve as a switch for MAPKAPK2 nuclear import and export. Phosphorylated MAPKAPK2 masks the nuclear localization signal at its C terminus by binding to p38. It unmasks the nuclear export signal, which is part of the second C-terminal helix packed along the surface of kinase domain C-lobe, and thereby carries p38 to the cytoplasm.

Selected figure(s)

Figure 1.
Fig. 1. Ribbon diagram of the MAPKAPK2 structure. The N-lobe of the kinase domain is colored light blue. The C-lobe of the kinase domain is colored dark blue. The regulatory domain is colored red. The key regulatory residue threonine 334 is labeled. The dotted line indicates the missing part of activation loop.

Figure 5.
Fig. 5. Interaction between the kinase domain C-lobe and the C-terminal regulatory domain second helix of MAPKAPK2.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 37401-37405) copyright 2002.

Figures were selected by an automated process.