1U54

Crystal Structures of the Phosphorylated and Unphosphorylated Kinase Domains of the CDC42-associated Tyrosine Kinase ACK1 bound to AMP-PCP

1U54 の概要

• エントリーDOI: 10.2210/pdb1u54/pdb
• 分子名称: Activated CDC42 kinase 1, MAGNESIUM ION, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, ... (5 entities in total)
• 機能のキーワード: tyrosine kinase, transferase
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cell membrane: Q07912 Q07912
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 67303.71

構造登録者

Lougheed, J.C.,Chen, R.H.,Mak, P.,Stout, T.J. (登録日: 2004-07-26, 公開日: 2004-08-31, 最終更新日: 2024-11-20)

主引用文献

Lougheed, J.C.,Chen, R.H.,Mak, P.,Stout, T.J.
Crystal Structures of the Phosphorylated and Unphosphorylated Kinase Domains of the Cdc42-associated Tyrosine Kinase ACK1.
J.Biol.Chem., 279:44039-44045, 2004

PubMed Abstract: ACK1 is a multidomain non-receptor tyrosine kinase that is an effector of the Cdc42 GTPase. Members of the ACK family have a unique domain ordering and are the only tyrosine kinases known to interact with Cdc42. In contrast with many protein kinases, ACK1 has only a modest increase in activity upon phosphorylation. We have solved the crystal structures of the human ACK1 kinase domain in both the unphosphorylated and phosphorylated states. Comparison of these structures reveals that ACK1 adopts an activated conformation independent of phosphorylation. Furthermore, the unphosphorylated activation loop is structured, and its conformation resembles that seen in activated tyrosine kinases. In addition to the apo structure, complexes are also presented with a non-hydrolyzable nucleotide analog (adenosine 5'-(beta,gamma-methylenetriphosphate)) and with the natural product debromohymenialdisine, a general inhibitor of many protein kinases. Analysis of these structures reveals a typical kinase fold, a pre-organization into the activated conformation, and an unusual substrate-binding cleft.

PubMed: 15308621
DOI: 10.1074/jbc.M406703200

実験手法

X-RAY DIFFRACTION (2.8 Å)