2NPQ

A Novel Lipid Binding Site in the p38 alpha MAP Kinase

2NPQ の概要

• エントリーDOI: 10.2210/pdb2npq/pdb
• 分子名称: Mitogen-activated protein kinase 14, octyl beta-D-glucopyranoside (3 entities in total)
• 機能のキーワード: lipid binding site, kinase, protein-lipid complex, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42827.89

構造登録者

Diskin, R.,Engelberg, D.,Livnah, O. (登録日: 2006-10-29, 公開日: 2007-10-16, 最終更新日: 2023-10-25)

主引用文献

Diskin, R.,Engelberg, D.,Livnah, O.
A novel lipid binding site formed by the MAP kinase insert in p38 alpha.
J.Mol.Biol., 375:70-79, 2008

PubMed Abstract: The p38 mitogen-activated protein (MAP) kinases function as signaling molecules essential for many cellular processes, particularly mediating stress response. The activity of p38 MAP kinases is meticulously regulated to reach the desired cellular phenotype. Several alternative activation and attenuation mechanisms have been characterized recently which include new phosphorylation sites. Here we present the crystal structure of p38 alpha MAP kinase in complex with n-octyl-beta-glucopyranoside detergent. The complex unveils a novel lipid-binding site formed by a local conformational change of the MAP kinase insert. This binding is the first attribution for a possible role of the MAP kinase insert in p38. The binding site can accommodate a large selection of lipidic molecules. In addition, we also show via biophysical methods that arachidonic acid and its derivatives bind p38 alpha in vitro. Based on our analysis we propose that the binding of lipids could fine-tune p38 alpha catalytic activity towards a preferred phenotype.

PubMed: 17999933
DOI: 10.1016/j.jmb.2007.09.002

実験手法

X-RAY DIFFRACTION (1.8 Å)