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ハリドイオン酸化中の人工ヘム変異. クロライドの酸化をホーレンラディッシュペロキシダゼによって実証
Liusheng Huang1, Grzegorz Wojciechowski, Paul R Ortiz de Montellano
1Department of Pharmaceutical Chemistry, University of California, 600 16th Street, San Francisco, California 94143-2280, USA.
Journal of the American Chemical Society
|April 14, 2005
まとめ
ホーラーラディッシュペロキシダゼ (HRP) は,現在,塩化物とブロミドを酸化し,改変したヘム群を形成することができます. この発見は,ペロキシダゼが独特の塩化物酸化能力を獲得するために最小限の変更が必要であることを示唆しています.
科学分野:
- バイオケミストリー バイオケミストリー
- 酵素学 酵素学とは
背景:
- ミエロペロキシダース (MPO),エオシノフィルペロキシダース (EPO),クロロペロキシダースは,ヒルラディッシュペロキシダース (HRP) などのほとんどのペロキシダースとは異なり,ハリドを酸化します.
- HRPは典型的にはヨウ素,時にはブロミドのみを酸化する.
研究 の 目的:
- HRPによるブロミド (Br-) と塩化物 (Cl-) の酸化を調査する.
- HRPによるハリド酸化のメカニズムと,ヘム変異への影響について調べる.
主な方法:
- Br-またはCl-と過酸化水素 (H2O2) で酸性pHでHRPのインキュベーション.
- ヘム群の改変を分析するための質量スペクトロメトリ.
- タンパク質のないヘム反応と中性pHの反応との比較.
主要な成果:
- HRPは酸性pHでブロミネーションを触媒化し,そのヘム群をブロミドで改変し,ブロモヒドリン添加物を形成します.
- メソクロアドクトを含む類似のヘム変異は,HRPがCl-およびH2O2.2と反応すると発生する.
- これらの変化は,pH値とHRPタンパク質の存在に依存しています.
結論:
- HRPは,Cl-を酸化する能力を初めて示した.
- HRPによるハリド酸化中の人工ヘム変異は,MPO/EPOのような活動のために最小限のタンパク質チューニングが必要であることを示唆しています.
- この研究は,MPOとEPOヘメスがハライド酸化過程で自己変異を回避する方法について疑問を投げかけています.
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