タイロシンフォスファタゼSHP-2の結晶構造
P Hof1, S Pluskey, S Dhe-Paganon
1Joslin Diabetes Center and the Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA.
Cell
|March 10, 1998
まとめ
SHP-2チロシンフォスファタゼは,SHP-2チロシンフォスファタゼという
科学分野:
- バイオケミストリー バイオケミストリー
- 構造生物学 構造生物学とは
- 酵素学 酵素学とは
背景:
- SHP-2は,細胞シグナル伝達に不可欠なタンパク質チロシンファスファターゼです.
- その活動は,下流の生物学的プロセスを制御するために厳格に規制されています.
研究 の 目的:
- SHP-2の触媒活動規制の構造的基礎を解明する.
- 酵素の抑制と活性化におけるSH2ドメインの役割を理解する.
主な方法:
- X線結晶学を用いて,SHP-2の構造を決定した.
- 高解像度構造分析 (2.0アングストーム) が実施されました.
主要な成果:
- N端のSH2ドメインは,リガンドがない場合,活性部位を遮断することで,直接的にフォスファタゼドメインを阻害する.
- N端のSH2ドメインへのリガンド結合は,形状の変化を誘導し,酵素を活性化します.
- C末端のSH2ドメインは,リガンド特異性と結合エネルギーに寄与するが,直接活性化には寄与しない.
結論:
- SHP-2はコンフォームスイッチとして機能し,そのN端のSH2ドメインによって制御されます.
- SHP-2構造は,フォスフォプロテイン結合による分子内抑制と活性化を含む,フォスファターゼ調節のための新しいメカニズムを明らかにします.
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