ニシン生物合成に関与するランチビオティック・サイクラスの構造とメカニズム

Bo Li¹, John Paul J Yu, Joseph S Brunzelle

¹Department of Biochemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL 61801, USA.

Science (New York, N.Y.)

|March 11, 2006

まとめ

研究者は,ニシンサイクラゼ (NisC) プロセスをインビトロで再構成し,そのX線結晶構造を決定しました. これは,NisCCを明らかにします.

科学分野:

バイオケミストリーバイオケミストリー
構造生物学構造生物学とは
微生物学微生物学とは

背景:

ニシンは広く使用されている食品保存剤であり,翻訳後に改変された抗微生物ペプチドとして認識されています.
ニシンの抗菌作用は,5つの周期性チオエーテル環を特徴とするユニークな構造に起因する.
これらのチオエーテル環を設置する酵素は,単一の酵素であるNisCで,複雑な改変を触媒化する.

研究の目的:

ニシンサイクライゼーションプロセスの in vitro 再構成を達成するために.
NisC酵素のX線結晶構造を決定する.
ニシン合成におけるチオエーテル環形成のメカニズムを解明する.

主な方法:

サイクル化プロセスを再構成するためのインビトロ生化学測定法.
X線結晶学により,NisC.の3次元構造を決定する.
機能的メカニズムを推論するために,既知の酵素との構造的比較.

主要な成果:

NisCによって触媒化されたニシンサイクル化反応の in vitro 再構成が成功しました.
NisC酵素の高解像度のX線結晶構造の決定.
構造分析により,保存された折りたたみと,哺乳類のファルネシル移転酵素と共有する基板活性化メカニズムが明らかになった.

結論:

NisC構造は,ニシンにおけるチオエーテル環形成の触媒機構の洞察を提供します.
特定された類似性は,NisCのヒトの同類体が,タンパク質基板に類似した翻訳後の改変を実行し,特にシステイン残留物を含む可能性があることを示唆しています.
この発見は,新しい抗微生物ペプチドとヒトタンパク質の改変経路の研究に新たな道を開く.

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