ラジカルS-アデノシル-l-メチオニンの反応におけるパラダイムシフト:オルガノメタリック中介物質 Ω は触媒の中心にある
Amanda S Byer1, Hao Yang2, Elizabeth C McDaniel1
1Department of Chemistry & Biochemistry , Montana State University , Bozeman , Montana 59717 , United States.
Journal of the American Chemical Society
|June 30, 2018
まとめ
ラジカルS-アデノシル-l-メチオニン (SAM) 酵素は,超家族全体の触媒に不可欠な新しい有機金属中間物質 Ω を利用する. この発見は SAM酵素の生物有機金属化学の理解を広げています
科学分野:
- 生物化学
- 酵素学
- バイオ・オルガン・メタリック・ケミストリー
背景:
- ラジカルS-アデノシル-l-メチオニン (SAM) 酵素は様々な生物学的反応に不可欠です.
- これらの酵素は,SAMの同解分解により,反応性のある5'-デオキシアデノシル基 (5'-dAdo·) を生成する.
- 以前は特徴づけられていなかった有機金属中間体 Ω が,ピルベートホルマトライアス活性化酵素 (PFL-AE) で観察された.
研究 の 目的:
- ラジカルSAM酵素スーパーファミリーにおける Ω 中間物質の広範な関連性を調査する.
- PFL-AEの触媒メカニズムにおける Ωの役割を決定する.
- Ω 中間物質の構造的性質と,その根本化学への影響について解明する.
主な方法:
- 基質の混合順序が異なる酵素運動の研究
- 電子パラマグネティック共振 (EPR) と電子核二重共振 (ENDOR) を含む光譜分析.
- さまざまな反応タイプを代表する様々なSAM酵素のパネルを比較した分析
主要な成果:
- Ω中間は触媒的に有能で,混合順にかかわらずPFL-AEで一貫して形成されます.
- 異なる反応クラスの複数の SAM 酵素で Ω 形成が確認されました.
- 顕微鏡データでは,Ω内のFe-C5'結合が,5'-dAdo·を [4Fe-4S]クラスタに結合し,同酵素B12に類似していることが明らかになった.
結論:
- Ω中間体は,SAM酵素スーパーファミリー全体で保存され,不可欠な特徴です.
- ΩにおけるFe-C5'結合は,急性反応を開始するための新しいバイオ・オルガノメタリックモチーフを表しています.
- この発見は,特に広範囲のSAM酵素スーパーファミリー内で,自然界における生物有機金属化学の既知の範囲を大幅に拡大します.
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