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Identification of Kinase-substrate Pairs Using High Throughput Screening
Published on: August 29, 2015
ミトスのロタマース Pin1 の構造と機能の分析は,基板認識がリン酸化に依存していることを示唆しています
R Ranganathan1, K P Lu, T Hunter
1Structural Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Cell
|June 13, 1997
まとめ
細胞循環の調節体であるPin1は,X線結晶学を用いて研究された. その構造は,細胞分裂に不可欠なペプチド結合イソメリゼーションのための酸塩および共振触媒を含む触媒機構を明らかにします.
科学分野:
- バイオケミストリー バイオケミストリー
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
背景:
- Pin1 (ペプチジルプロリルシストランスイソメラーゼ) は,細胞サイクル,特にG2/M移行の重要な調節剤です.
- ミトーシスにおけるその役割は,真核細胞分裂におけるその重要性を強調しています.
研究 の 目的:
- 人間の構造的,機能的特性を解明する Pin1.
- Pin1.1の触媒機構と基板結合の好みを理解する.
主な方法:
- X線結晶学を使用して,AlaProダイペプチドで複合されたPin1の1.35 Åの結晶構造を決定しました.
- 機能的特徴付けには,pH値の定位試験と活性部位システイン変異作用が含まれていました.
主要な成果:
- 結晶構造は,Pin1とAlaProの複合体を明らかにし,その活性部位の洞察を提供しました.
- 触媒メカニズムは,ペプチド結合イソメリゼーションのための一般的な酸塩および共振触媒を含みます.
- Pin1は,プロリン結合のN端の酸性残留を好み,基本的なクラスターと相互作用する.
結論:
- この発見は,Pin1のイソメラーゼ活性に対する詳細な触媒メカニズムを示唆しています.
- 観察された基板の好みは,細胞サイクル制御におけるPin1基板の相互作用のリン酸化媒介調節の可能性を示しています.
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