2機能のRelA/SpoTホモログの反対の活性部位間のコンフォーメーションアンタゴニズムは,厳格な応答中の (p) ppGpp代謝を調節する[修正]
Tanis Hogg1, Undine Mechold, Horst Malke
1Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Cell
|April 7, 2004
まとめ
バクテリアは,Rel/Spo酵素によって調節される厳格な応答を使用して,栄養素の不足を生き延びます. 構造分析は,これらの酵素がアラモンの合成と水解の間でどのように切り替わっているかを明らかにします (p) pGpp.
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.
- 構造生物学 構造生物学とは
背景:
- Rel/Spo酵素はアラームホルモン (p) ppGppを生成し,栄養素の制限に対する細菌の厳格な反応を誘発する.
- この反応は,飢餓中の細菌の生存に極めて重要です.
- Rel/Spoタンパク質は,合成および水解 (p) pGpp. を行うバイ機能的触媒活性を有しています.
研究 の 目的:
- Rel/Spo酵素活動の相互調節の構造的基礎を解明する.
- 厳格な反応のメカニズムを分子レベルで理解する.
主な方法:
- Streptococcus dysgalactiae亜種からのRel/Spo同型Rel (((Seq) のX線結晶学で撮影したものです. エクシシミリス (equisimilis) とは
- 酵素構成と活性サイト構造の分析.
- サイト・ディレクテッド・ミュータゲネシスで,酵素調節を調査する.
主要な成果:
- 2.1 Åの結晶構造は,合成酵素-ON/ヒドロラゼ-OFF状態と合成酵素-OFF/ヒドロラゼ-ON状態に対応する2つの異なる酵素構成を明らかにした.
- 水酸化酵素と合成酵素ドメインは,周期性リン酸エステル酶と核チルトランスフェラーゼのスーパーファミリーと類似性を共有しています.
- 活性部位は遠く離れていても繋がっており,GDP-2':3'-サイクル単リン酸を含む結合核酸が結合しています.
- ミュタゲネシスは,リガンド誘発信号伝送を含む相互調節をサポートしました.
結論:
- この構造は,Rel/Spo酵素活動の相互調節のための分子基盤を提供します.
- 活性部位間のリガンド誘発信号伝達は,厳格な応答を制御している可能性が高い.
- このメカニズムを理解することで,細菌の生存メカニズムを標的とした戦略を策定することができます.
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