メタロ酸化酵素Fet3pのネイティブ中間物の急速な分解は,効率的な代謝のための制御されたFeII酸化を可能にします
Stephen M Jones1, David E Heppner1, Kenny Vu2
1Department of Chemistry, Stanford University, 333 Campus Drive Stanford, California 94305, United States.
Journal of the American Chemical Society
|May 8, 2020
まとめ
マルチコッパー酸化剤 (MCO) は,様々な回転頻度を示しています. この研究は,原生中介体への陽子の供給が,鉄代謝と反応性酸素種発生を防ぐために不可欠なFet3pの遅い周回を制御することを明らかにしています.
科学分野:
- 生物化学
- 酵素学
- メタロプロテイン化学
背景:
- 多銅酸化酵素 (MCOs) は,酸素還元と結合した基板酸化を触媒化する.
- MCOは基板特異性およびターンオーバー周波数 (TOF) によって分類される.有機基板には高TOF,金属イオンには低TOFがある.
- 高TOFの有機酸化酵素の触媒メカニズムは,安定したネイティブ中間物質 (NI) に急速な分子内電子移転 (IET) を含む.
研究 の 目的:
- メタルオキシダゼであるFet3pにおける低TOFを制御する要因を解明する.
- Fet3pの触媒メカニズムにおける速度制限ステップを理解する.
- 鉄代謝におけるFet3p機能の触媒モデルを開発する.
主な方法:
- Fet3pの触媒サイクルに関するメカニズム的調査.
- 電子の移転と中断の運動分析
- 触媒モデルの開発と応用
主要な成果:
- Fet3pの原産中間物質 (NI) は,ターンオーバー条件下で急速に分解する.
- Fet3pの触媒サイクルは,静止酵素へのゆっくりとした分子内電子伝達 (IET) によって速度制限されます.
- FET3pのメカニズムと流通率を制御する重要な規制ステップとして,NIへのプロトンの配送が特定されています.
結論:
- 陽子の納入はFet3pの遅いターンオーバーメカニズムに左右されます.
- 鉄の効率的な代謝には機能的に重要なものです
- このメカニズムは,鉄の酸化中に反応性酸素種 (ROS) の生成を防止します.
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