AlbAの構造と機能によって明らかにされた細菌の多剤耐性システムの適応

Asfandyar Sikandar¹, Katarina Cirnski^2,3, Giambattista Testolin^3,4

¹Workgroup Structural Biology of Biosynthetic Enzymes, Helmholtz Institute for Pharmaceutical Research Saarland , Helmholtz Centre for Infection Research, Saarland University , Campus Geb. E8.1 , Saarbrücken 66123 , Germany.

Journal of the American Chemical Society

|November 14, 2018

まとめ

新しい研究は,抗生物質を中和するタンパク質 AlbA が,抗生物質アルビシジンに結合し,それを変化させる方法を明らかにしています. このタンパク質は古代の遺伝子から進化し抗生物質耐性メカニズムや新薬発見戦略の可能性を洞察しました

科学分野:

微生物学
構造生物学
薬物の発見

背景:

抗菌剤耐性には新しい抗生物質の発見が必要です
アルビシジンとシストバクタミッドは,グラム陽性およびグラム陰性病原体に対して有効な強力な抗生物質です.
アルビシジン中和タンパク質A (AlbA) は潜在的な抵抗メカニズムである.

研究の目的:

アルビシジンとの相互作用の構造的基礎を解明する.
AlbAがアルビシジンを中和するメカニズムを理解する.
アルバの進化の起源を調査する

主な方法:

アルビシジンの構造と複合体を決定するX線結晶学.
アルビシジンの改変を証明する生化学的測定
生物情報分析により進化の関係を推測する

主要な成果:

AlbAの構造は2つのドメインを明らかにし,それぞれが多抗生物質中和タンパク質 TipAに似ています.
アルビシジンの結合は,両方の AlbA ドメインに擬似的に分布した.
AlbAはアルビシディンの予期せぬ化学変化を促し,その効力を低下させます.

結論:

AlbAは,内部複製を通して,古代のTipAのような遺伝子から進化した可能性がある.
この発見は,アルビシジン中和と耐性の構造的な理解を提供します.
この研究は抗生物質結合タンパク質の進化と新しい抗生物質の開発の可能性についての洞察を提供します

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