PDBsum entry 3e7o

Transferase

PDB id: 3e7o

Contents

Protein chains

342 a.a.

Ligands

35F ×2

Waters ×251

References listed in PDB file

Key reference

Title

The crystal structure of jnk2 reveals conformational flexibility in the map kinase insert and indicates its involvement in the regulation of catalytic activity.

Authors

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

Ref.

J Mol Biol, 2008, 383, 885-893. [DOI no: 10.1016/j.jmb.2008.08.086]

PubMed id

18801372

Note In the PDB file this reference is annotated as "TO BE PUBLISHED". The citation details given above were identified by an automated search of PubMed on title and author names, giving a perfect match.

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.

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.