酸化窒素とメトミオグロビンの可逆結合に関するメカニズム研究
L E Laverman1, A Wanat, J Oszajca
1Contribution from the Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106, USA.
Journal of the American Chemical Society
|July 18, 2001
まとめ
メトミオグロビン (metMb) は,酸化窒素 (NO) を逆向きに結合し,ニトロシルアドクトを形成する. 運動学的研究により,NOの結合と放出の両方に対する解離的メカニズムが明らかにされ,体積とエントロピーの有意な変化が見られる.
科学分野:
- バイオケミストリー バイオケミストリー
- 化学動力学 化学動力学
- タンパク質-リガンドの相互作用
背景:
- メトミオグロビン (metMb) はフェリヘムタンパク質である.
- 酸化窒素 (NO) はバイオメッセンジャー分子である.
- メトミオグロビンは,生理学的pHでNOを逆結合してニトロシル添加物 (metMb(NO)) を形成します.
研究 の 目的:
- 酸化窒素とメトミオグロビンとの結合と解離の運動学を調査する.
- これらの反応の活性化パラメータ (DeltaH,DeltaS,DeltaV) を決定する.
- NOがメトミオグロビンと結合する反応メカニズムを解明する.
主な方法:
- レーザーフラッシュフォトリシス
- ストップフロー運動学
- 高圧研究 高圧研究
- NO トラッピングの実験
主要な成果:
- アソシエーション反応 (metMb + NO) は活性化パラメータを示した:DeltaH (オン) ≈65 kJ/mol,DeltaS (オン) ≈60 J/mol·K,DeltaV (オン) ≈20 cm3/mol.
- 分離反応 (metMb(NO)) の活性化パラメータは,DeltaH(off) = 76 kJ/mol,DeltaS(off) ≈ 41 J/mol·K,およびDeltaV(off) = 20 cm3/molでした.
- "オン"反応の大きな陽性DeltaSとDeltaV値は,水の先行解離を含む解離性リガンド置換メカニズムを示唆する.
結論:
- NOとメトミオグロビンとの結合と解離は,制限解離的メカニズムに従う.
- 第6コーディネーションサイトからの水の放出は,NOの拘束に先立ちます.
- この発見は,モデルシステムおよび他の金属タンパク質に関する研究と一致しています.
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