モノニトロシル鉄複合体をシステインアナログによって [2Fe-2S] クラスタに変換する
Jessica Fitzpatrick1, Harris Kalyvas, Milos R Filipovic
1Department of Chemistry, Brown University , Providence, Rhode Island 02912, United States.
Journal of the American Chemical Society
|May 9, 2014
まとめ
研究者らは,酸化窒素 (NO) によって損傷した鉄硫黄 [Fe-S] クラスタを修復するための新しい方法を実証しました. このプロセスは,モノニトロシル鉄複合体 (MNIC) をシステインアナログを使用して,機能的な[Fe-S]クラスタに戻します.
科学分野:
- バイオ・オーガニック化学 バイオ・オーガニック化学
- バイオケミストリー バイオケミストリー
- メタロタンパク質化学 メタロタンパク質化学
背景:
- 酸化窒素 (NO) は,制御タンパク質の鉄硫黄 (Fe-S) クラスタを逆転的に変異させ,遺伝子スイッチとして作用します.
- NO誘発 [Fe-S] クラスタの改変は十分に研究されているが,これらのクラスタを修復する逆のプロセスは依然として十分に理解されていない.
研究 の 目的:
- 酸化窒素で損傷した[Fe-S]クラスターの修復メカニズムを調査する.
- システインアナログを使用して,モノニトロシル鉄複合体 (MNIC) を [2Fe-2S] クラスタに戻す変換を実証する.
主な方法:
- 特定のMNIC, (PPN) [Fe(S(t) Bu) 3(NO) ] (1),を, (PPN) 2[Fe2S2(SCH2CH2C(O) OMe) [4] (2) の [2Fe-2S]クラスタに,3-メルカプトメチルプロピオネート (MMP) を加えることで変換する.
- 発生したクラスタの特徴は,スペクトロスコピー,化学,結晶学,分析方法を用いて決定する.
- マススペクトロメトリーと (34) Sラベリングを使用して,ブリッジング硫化物の起源を追跡し,NO捕獲メカニズムを特定します.
主要な成果:
- 室温でMMPのみを添加することで,MNIC (1) を [2Fe-2S] クラスタ (2) に成功裏に変換しました.
- 顕微鏡,化学,結晶,および分析データにより,合成された [2Fe-2S] クラスタのアイデンティティが確認されました.
- 質量スペクトロメトリーと (34) Sラベリングは,MMPが修復されたクラスタのためのブリッジング硫化物を提供することを示しました.
- 放出されたNOは,ダイニトロシル鉄複合体の副産物 (PPN) [Fe ((SCH2CH2C ((O) OMe)) 2 ((NO)) 2) ] (4) に効果的に閉じ込められました.
結論:
- モノニトロシル鉄複合物 (MNIC) は,NOで損傷した [2Fe-2S] クラスタの修復における中間物質である可能性が高い.
- システインとその類型は,MNICを不安定化し, [2Fe-S] クラスターの形成を促進する活性の高い分子です.
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