プチダレドキシンがシトクロームP450カムに与える影響
Shu-Hao Liou1, Mavish Mahomed1, Young-Tae Lee1
1Department of Chemistry, University of California, Davis , One Shields Avenue, Davis, California 95616, United States.
Journal of the American Chemical Society
|July 26, 2016
まとめ
プチダレドキシン (Pdx) の結合は,サイトクロームP450カムの構成に影響を与え,それを開いた状態に移動させます. しかし,P450camへの一酸化炭素結合は,Pdx状態に関係なく,この形状の変化を防ぐ.
科学分野:
- 生物化学
- 構造生物学
- バイオ物理学
背景:
- サイトクロームP450カムは,そのレドックスパートナーであるプチダレドキシン (Pdx) によって影響される形状の変化を経験します.
- EPRと結晶学を用いた以前の研究では,Pdxが基質に結合したP450camのオープンコンフォーメーションを誘導することを示唆したが,DEERとNMRのデータは矛盾した結果を示した.
研究 の 目的:
- スピンラベリングとDEERスペクトロスコーピーを用いて,サイトクロームP450カムの構成におけるPdxのエフェクターの役割を明らかにする.
- リガンド結合 (CO) とPdx酸化状態がP450カムの形状に及ぼす影響を調査する.
主な方法:
- P450camのFおよびGヘリクにMTSLまたはBSLでサイト向けスピンラベルを貼る.
- 二重電子共振 (DEER) スペクトルによる距離測定
- オープンフォームのP450camの結晶構造の分析
主要な成果:
- 酸化されたPdxは,MTSLで標識されたカンファー結合P450カムの閉ざされた形状のシフトを誘導する.
- FまたはGヘリクスのバイ機能スピンラベル (BSL) は,距離分布と形状の変化を調節した.
- 混合状態の複合体のDEERスペクトル (酸化Pdx,鉄性CO結合P450cam) は,P450camが閉ざされたままであることを示した.
- オープンフォームのP450camの結晶構造は,結晶パッキングの潜在的な効果を明らかにしました.
結論:
- Pdx結合はP450カムの形状に影響するが,ヘムへのCO結合は,閉じた状態を維持し,この効果を無効にする.
- DEER光譜は,Pdxとリガンド状態に依存するP450カムの構成動態に関する貴重な洞察を提供します.
- 構造データを解釈する際には,結晶包装による潜在的なアーティファクトを考慮する必要があります.
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