MURJ機能には膜ポテンシャルが必要である
Frederick A Rubino1, Sujeet Kumar2, Natividad Ruiz2
1Department of Chemistry and Chemical Biology , Harvard University , Cambridge , Massachusetts 02138 , United States.
Journal of the American Chemical Society
|March 21, 2018
まとめ
新種の抗生物質は,グラム陰性感染症において,MURJ (フリッパース) を標的とする. 研究者は,抗生物質の開発を支援する,脂質II蓄積を測定することによって,MurJ阻害を定量化するための新しい測定法を開発しました.
科学分野:
- 微生物学
- 生物化学
- 薬物の発見
背景:
- MurJは,細胞壁の重要な成分である脂質IIの輸出に不可欠な細菌のフリッパースです.
- グラム陰性細菌に対する 新しい抗生物質の開発は 医学的に満たされていない 重要なニーズです
- 輸送中に基質の化学的変化がないため,MurJ活性を定量化するための既存の方法は限られています.
研究 の 目的:
- MurJフリッパース活性をモニタリングするための定量分析を開発する.
- MurJ機能を阻害する条件と化合物を特定します.
- 抑制に対する反応としてMurJの形状の変化を理解する.
主な方法:
- MurJ抑制の指標として,細胞内リピドIIの蓄積を定量化するために,バイオチンタグの戦略が採用された.
- このアッセイは,膜ポテンシャルがMurJ活性に及ぼす影響をテストするために使用された.
- MurJ構造を分析するためにシステインアクセシビリティの探査が行われました.
主要な成果:
- 細胞内脂質IIの蓄積を測定することで,新しい測定法でMurJ抑制を成功裏に定量化しました.
- 膜ポテンシャルを消散する化合物により,MurJの活性が抑制された.
- 膜ポテンシャル消去による阻害により,MurJは不活性で外向きの形状を採用した.
結論:
- 膜ポテンシャルは,E. coliにおけるMurJ機能に不可欠である.
- 開発された測定法により,MurJ阻害剤の定量化が可能である.
- MurJの非活性で外向きの形状は,新しい抗生物質の設計のための構造的ターゲットを提供します.
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