4BFM

The crystal structure of mouse PK38

4BFM の概要

• エントリーDOI: 10.2210/pdb4bfm/pdb
• 分子名称: MATERNAL EMBRYONIC LEUCINE ZIPPER KINASE, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: transferase
• 由来する生物種: MUS MUSCULUS (HOUSE MOUSE)
• 細胞内の位置: Cell membrane; Peripheral membrane protein (By similarity): Q61846
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 39823.39

構造登録者

Yoo, J.H.,Cho, Y.S.,Park, S.M.,Cho, H.S. (登録日: 2013-03-21, 公開日: 2014-02-12, 最終更新日: 2023-12-20)

主引用文献

Cho, Y.S.,Yoo, J.,Park, S.,Cho, H.S.
The Structures of the Kinase Domain and Uba Domain of Mpk38 Suggest the Activation Mechanism for Kinase Activity.
Acta Crystallogr.,Sect.D, 70:514-, 2014

PubMed Abstract: Murine protein serine/threonine kinase 38 (MPK38) is the murine orthologue of human maternal embryonic leucine-zipper kinase (MELK), which belongs to the SNF1/AMPK family. MELK is considered to be a promising drug target for anticancer therapy because overexpression and hyperactivation of MELK is correlated with several human cancers. Activation of MPK38 requires the extended sequence (ExS) containing the ubiquitin-associated (UBA) linker and UBA domain and phosphorylation of the activation loop. However, the activation mechanism of MPK38 is unknown. This paper reports the crystal structure of MPK38 (T167E), which mimics a phosphorylated state of the activation loop, in complex with AMP-PNP. In the MPK38 structure, the UBA linker forces an inward movement of the αC helix. Phosphorylation of the activation loop then induces movement of the activation loop towards the C-lobe and results in interlobar cleft closure. These processes generate a fully active state of MPK38. This structure suggests that MPK38 has a similar molecular mechanism regulating activation as in other kinases of the SNF1/AMPK family.

PubMed: 24531485
DOI: 10.1107/S1399004713027806

実験手法

X-RAY DIFFRACTION (2.35 Å)