サクティペプチドの生物合成におけるチオエーテル結合形成に関する構造的洞察
Tyler L Grove1, Paul M Himes2, Sungwon Hwang2
1Department of Biochemistry, Albert Einstein College of Medicine , Bronx, New York 10461, United States.
Journal of the American Chemical Society
|July 14, 2017
まとめ
この研究は,サクチオニペプチド生物合成における重要な酵素であるCteBの構造を明らかにしています. この構造を理解することで,抗生物質における必須のチオエーテル結合の形成のための SAM 酵素メカニズムに光を当てることができます.
科学分野:
- 生物化学
- 構造生物学
- 微生物学
背景:
- サクチペプチドは,活性化のために翻訳後のチオエーテルブリッジ (サクチオイン結合) を必要とする抗生物質である.
- このユニークな結合は,ラジカルベースの化学と複数の [4Fe-4S] クラスターを利用したラジカル SAM 酵素によって形成されます.
研究 の 目的:
- サクチオン結合形成酵素CteBの高解像度結晶構造を決定する.
- サクチオン結合形成の構造的基礎とドメインの役割を解明する.
主な方法:
- CteBの構造を得るためにX線結晶学を用いた.
- 構造は2.04 Å解像度で解け,SAMとペプチジル基板断片で共結晶化された.
主要な成果:
- 構造は,CteBが (β/α) 6-TIMバレルの折りたたみと2つの [4Fe-4S]クラスターを持つC端のSPASMドメインを持っていることを示している.
- 重要な発見は,ダイナミックな調整サイトを持つSPASM領域の補助 [4Fe-4S]クラスタです.
- RiPP前駆ペプチド認識要素 (RRE) に類似するN端領域が特定されました.
結論:
- これはサクチオニン結合形成酵素の最初の結晶構造であり,急進的なSAM酵素機構に関する重要な洞察を提供します.
- この構造は,CteBが [4Fe-4S] クラスターと基板結合部位をどのように用いてチオエーテル結合形成を触媒化するかを説明する.
- AlbAやThnBのような関連酵素を理解し,新たな抗生物質を設計するのに役立つでしょう.
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