PDBsum entry 3e7o

Transferase

PDB id: 3e7o

Contents

Protein chains

342 a.a. *

Ligands

35F ×2

Waters ×251

* Residue conservation analysis

PDB id:

3e7o

Name:

Transferase

Title:

Crystal structure of jnk2

Structure:

Mitogen-activated protein kinase 9. Chain: a, b. Fragment: residues 7-362. Synonym: stress-activated protein kinase jnk2, c-jun n-terminal kinase 2, jnk-55. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: mapk9, jnk2, prkm9. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.14Å R-factor: 0.219 R-free: 0.250

Authors:

A.Kuglstatter,A.G.Villasenor

Key ref:

D.Shaw et al. (2008). The crystal structure of JNK2 reveals conformational flexibility in the MAP kinase insert and indicates its involvement in the regulation of catalytic activity. J Mol Biol, 383, 885-893. PubMed id: 18801372 DOI: 10.1016/j.jmb.2008.08.086

Date:

18-Aug-08 Release date: 09-Sep-08

Protein chains

P45984  (MK09_HUMAN) -  Mitogen-activated protein kinase 9 from Homo sapiens

Seq: 424 a.a.

Struc: 342 a.a.*

* PDB and UniProt seqs differ at 6 residue positions (black crosses)

Enzyme reactions

• Enzyme class: 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: 10.1016/j.jmb.2008.08.086

J Mol Biol 383:885-893 (2008)

PubMed id: 18801372

The crystal structure of JNK2 reveals conformational flexibility in the MAP kinase insert and indicates its involvement in the regulation of catalytic activity.

D.Shaw, S.M.Wang, A.G.Villaseñor, S.Tsing, D.Walter, M.F.Browner, J.Barnett, A.Kuglstatter.

ABSTRACT

c-Jun N-terminal kinase (JNK) 2 is a member of the mitogen-activated protein (MAP) kinase group of signaling proteins. MAP kinases share a common sequence insertion called "MAP kinase insert", which, for ERK2, has been shown to interact with regulatory proteins and, for p38alpha, has been proposed to be involved in the regulation of catalytic activity. We have determined the crystal structure of human JNK2 complexed with an indazole inhibitor by applying a high-throughput protein engineering and surface-site mutagenesis approach. A novel conformation of the activation loop is observed, which is not compatible with its phosphorylation by upstream kinases. This activation inhibitory conformation of JNK2 is stabilized by the MAP kinase insert that interacts with the activation loop in an induced-fit manner. We therefore suggest that the MAP kinase insert of JNK2 plays a role in the regulation of JNK2 activation, possibly by interacting with intracellular binding partners.

Selected figure(s)

Figure 2.
Fig. 2. Ribbon representation of JNK2. The Gly-rich loop is indicated in red, the hinge sequence in blue, helix αC in cyan, and the activation loop in magenta. Exchanged surface residues are colored green.

Figure 4.
Fig. 4. Intermolecular crystal interactions of exchanged residues. (a) S177 and (b) A251 and adjacent residues are colored yellow, and residues of the contacting protein in the crystal are colored gray. Hydrogen bonds are indicated as dotted lines, and van der Waals interactions are indicated as continuous lines.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2008, 383, 885-893) copyright 2008.

Figures were selected by an automated process.