2AC3

Structure of human Mnk2 Kinase Domain

2AC3 の概要

• エントリーDOI: 10.2210/pdb2ac3/pdb
• 関連するPDBエントリー: 2AC5
• 分子名称: MAP kinase-interacting serine/threonine kinase 2, ZINC ION (3 entities in total)
• 機能のキーワード: dfd motif, 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: 35727.90

構造登録者

Jauch, R.,Wahl, M.C.,Netter, C.,Jakel, S.,Schreiter, K.,Aicher, B.,Jackle, H. (登録日: 2005-07-18, 公開日: 2005-10-04, 最終更新日: 2024-03-13)

主引用文献

Jauch, R.,Jakel, S.,Netter, C.,Schreiter, K.,Aicher, B.,Jackle, H.,Wahl, M.C.
Crystal structures of the Mnk2 kinase domain reveal an inhibitory conformation and a zinc binding site.
Structure, 13:1559-1568, 2005

PubMed Abstract: Human mitogen-activated protein kinases (MAPK)-interacting kinases 1 and 2 (Mnk1 and Mnk2) target the translational machinery by phosphorylation of the eukaryotic initiation factor 4E (eIF4E). Here, we present the 2.1 A crystal structure of a nonphosphorylated Mnk2 fragment that encompasses the kinase domain. The results show Mnk-specific features such as a zinc binding motif and an atypical open conformation of the activation segment. In addition, the ATP binding pocket contains an Asp-Phe-Asp (DFD) in place of the canonical magnesium binding Asp-Phe-Gly (DFG) motif. The phenylalanine of this motif sticks into the ATP binding pocket and blocks ATP binding as observed with inhibitor bound and, thus, inactive p38 kinase. Replacement of the DFD by the canonical DFG motif affects the conformation of Mnk2, but not ATP binding and kinase activity. The results suggest that the ATP binding pocket and the activation segment of Mnk2 require conformational switches to provide kinase activity.

PubMed: 16216586
DOI: 10.1016/j.str.2005.07.013

実験手法

X-RAY DIFFRACTION (2.1 Å)