生物学的バッファーである二酸化炭素/CO2は,H2O2媒介によるタンパク質チロシンフォスファタゼの不活性化を強化する
Haiying Zhou1, Harkewal Singh, Zachary D Parsons
1Department of Chemistry, University of Missouri, Columbia, Missouri 65211, United States.
Journal of the American Chemical Society
|September 15, 2011
まとめ
過酸化水素 (H2O2) は,タンパク質チロシンフォスファタゼ (PTP) を in vitro でゆっくりと無効化する. ビカルボネート/CO2バッファーは,H2O2を強化する.
科学分野:
- バイオケミストリー バイオケミストリー
- 細胞シグナル伝達 細胞信号伝達
- 構造生物学 構造生物学とは
背景:
- 過酸化水素 (H2O2) は,重要な細胞シグナリング分子として作用します.
- H2O2は,タンパク質チロシンフォスファタゼ (PTP) の触媒的なシステイン残基を酸化することによって,それを無効化する.
- H2O2によるPTP不活性化は,細胞シグナル伝達において迅速であるが,in vitroでは遅い.
研究 の 目的:
- H2O2によるPTP無活性化率の不一致の背後にあるメカニズムを in vitro vs. in vivo で調査する.
- H2O2媒介のPTP不活性化を潜在化する要因を特定する.
- PTPに対するH2O2の作用を調節する生物学的バッファーの役割を明らかにする.
主な方法:
- PTPの活性と不活性化運動を測定するための生化学的測定法.
- PTPの高解像度の結晶分析.
- 異なる濃度の過酸化水素と二酸化炭素/CO2バッファーを用いたインビトロ実験.
主要な成果:
- 生物学的バッファーである二酸化炭素/CO2は,PTPのH2O2.2による無活性化を著しく強化する.
- H2O2とバイカーボネート/CO2の反応により,ペロキシモノカーボネートが生成されます.
- 結晶学的データは,ペロキシモノカーボネートがPTPの触媒システインを酸化するメカニズムを支持しています.
結論:
- ビカルボネート/CO2バッファは,ペロキシモノカーボネート形成を通じて,H2O2誘発のPTP不活性化を強化する.
- この発見は,インビトロ条件と比較して,細胞シグナル伝達において観察されたより速いPTP不活性化を説明します.
- この研究は,生物学的システムにおけるPTP活性を調節する新しいメカニズムを明らかにしています.
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