陽子による酸素-酸素結合分裂が,シトクロームp450における酸素-酸素結合分裂を助長する
André R Groenhof1, Andreas W Ehlers, Koop Lammertsma
1Vrije Universiteit, FEW, Department of Chemistry, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.
Journal of the American Chemical Society
|April 20, 2007
まとめ
プロトネーションは,シトクロームP450水素ペロキソ化合物0.0におけるO-O結合分裂に影響する. このプロトン転送は,鉄酸化化合物Iへの変換を調節し,酸化経路に影響を与えます.
科学分野:
- バイオケミストリー バイオケミストリー
- コンピューティング・ケミストリー
- 酵素のメカニズム
背景:
- サイトクロームP450は,様々な代謝プロセスに関与する重要な酵素です.
- 触媒のサイクル,特にO-O結合の割れ方のステップを理解することは,それらの機能を明らかにする鍵です.
- ヒドロペロキソ化合物0は,P450の触媒サイクルにおける重要な中間物質である.
研究 の 目的:
- サイトクロームP450水素ペロキソ化合物0.0におけるプロトンの補助によるO−O結合分裂のメカニズムを調査する.
- 化合物0から化合物Iへの変換のエネルギー障壁と熱力学的好意性を決定する.
- P450の触媒サイクルにおけるプロトネーションの調節作用を探求する.
主な方法:
- 反応経路をモデル化するために,密度関数理論 (DFT) の計算を使用した.
- この研究では,陽子源の酸性のO−O結合分裂障壁に対する影響を分析した.
- 隣接鉄のヘム・リガンドプロトネーションが反応エネルギーに与える影響を調査した.
主要な成果:
- 化合物0から鉄酸化化合物Iの形成に計算上の障壁が特定されました.
- O-O結合分裂バリアとエンド熱性は,遠端陽子源が酸性低下するにつれて増加する.
- 隣接鉄のヘムリンガンドのプロトン化により,O-O結合の分裂が容易になる.
- 化合物0から化合物Iへの変換は,過酸化酵素とカタラーゼモデルではわずかにエクソテルミックである.
結論:
- 陽子伝達は,P450sにおけるO−O結合の分裂を調節する上で重要な役割を果たします.
- 陽子源の酸性とヘムリガンドの陽子化が,触媒サイクルを制御する重要な要因である.
- 化合物0と化合物Iの間のエネルギー関係は,潜在的な酸化経路に影響を与える.
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