5B2K

A crucial role of Cys218 in the stabilization of an unprecedented auto-inhibition form of MAP2K7

5B2K の概要

• エントリーDOI: 10.2210/pdb5b2k/pdb
• 関連するPDBエントリー: 5B2L 5B2M
• 分子名称: Dual specificity mitogen-activated protein kinase kinase 7 (2 entities in total)
• 機能のキーワード: protein kinase, apo structure, auto-inhibition form, 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: 36998.90

構造登録者

Sogabe, Y.,Hashimoto, T.,Matsumoto, T.,Kirii, Y.,Sawa, M.,Kinoshita, T. (登録日: 2016-01-19, 公開日: 2016-04-06, 最終更新日: 2023-11-08)

主引用文献

Sogabe, Y.,Hashimoto, T.,Matsumoto, T.,Kirii, Y.,Sawa, M.,Kinoshita, T.
A crucial role of Cys218 in configuring an unprecedented auto-inhibition form of MAP2K7
Biochem.Biophys.Res.Commun., 473:476-481, 2016

PubMed Abstract: Mitogen-activated protein kinase kinase 7 (MAP2K7) is an indispensable kinase of the c-Jun N-terminal kinase signal cascade and is rigorously regulated via phosphorylation. To investigate the regulatory mechanism of the inactive non-phosphorylated state of MAP2K7, the crystal structures of the wild-type and C218S mutant were solved. The wild-type apo-structure revealed an unprecedented auto-inhibition form that occluded the ATP site. This closed form was configured by the n-σ* interaction of Cys218, a non-conserved residue among the MAP2K family kinases, with Gly145 in the glycine-rich loop. The interaction was unaltered in the presence of an ATP analog, whereas the C218S mutation precluded the closed configuration. These structural insights are potentially valuable for drug discovery of highly selective MAP2K7 inhibitors.

PubMed: 26987717
DOI: 10.1016/j.bbrc.2016.03.036

実験手法

X-RAY DIFFRACTION (2.75 Å)