設計された超分子タンパク質組成体で, in vivo 酵素活性がある
1Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0356, USA.
Science (New York, N.Y.)
|December 20, 2014
まとめ
科学者たちは,関係のないタンパク質を組み立てることで,新しい人工メタロベータ・ラクタマースを作りました. この酵素は,E. coliがアンピシリンに耐性を持つことを可能にし,酵素設計の新たなアプローチを示しています.
科学分野:
- タンパク質エンジニアリングは,
- 合成生物学 合成生物学とは
- 酵素触媒は,酵素を触媒として用いる.
背景:
- 新しく機能性タンパク質を設計することは,大変な課題です.
- 既存の方法は,しばしばタンパク質の内部を再利用します.
- 人工酵素は,新しいアプリケーションに不可欠です.
研究 の 目的:
- 機能する人工メタロベータ・ラクタマゼを設計する.
- 触媒作用のための de novo タンパク質組成を実証する.
- 抗生物質耐性に対する生物触媒を作る.
主な方法:
- モノメア・レドックスタンパク質のセルフ・アセンブリをテトラメア構造にします.
- タンパク質のインターフェイスに触媒性亜鉛部位を組み込む.
- Escherichia coli.におけるインビボ機能性スクリーニング
主要な成果:
- 機能的な人工メタロベータラクタマースが作られました.
- この酵素は,E. coliに対するアンピシリンの耐性をもたらした.
- 一種の変種はアンピシリンの水解に対する高触媒能力 (2.3 × 10^6) を示した.
- アクティブサイトは,基板の相互作用のための移動ループを進化させた.
結論:
- デノボのタンパク質組成は,新しい酵素活性を生成することができます.
- このアプローチは,酵素設計のための新しいパラダイムを提供します.
- エンジニアリングされた酵素は,天然のベータ・ラクタマースの特徴を模倣しています.
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