熱愛性インドールグリセロールリン酸塩合成の基底状態の計算による研究:温度による活性部位における構造変化

Devleena Mazumder-Shivakumar¹, Kalju Kahn, Thomas C Bruice

¹Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, California 93106, USA.

Journal of the American Chemical Society

|May 13, 2004

まとめ

超熱性インドル-3-グリセロールリン酸合成酵素 (IGPS) の活性度は,より反応性の高い酵素基板コンフォマーにより,温度とともに増加する. この研究は,温度を明らかにします.

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
コンピュータ生物学コンピュータ生物学

背景:

超熱性インドル-3-グリセロールリン酸合成酵素 (IGPS) は,トリプトファン生物合成に不可欠です.
異なる温度での酵素基板動態を理解することは,酵素の機能の鍵です.

研究の目的:

温度による酵素基板複合体の構造変化を調査する.
反応性コンフォマー群と反応速度を相関させるため.

主な方法:

分子動力学 (MD) シミュレーションは,酵素結合基板に298Kと385Kで実施されました.
シミュレーションにはCHARMMの力場とTIP3Pの水モデルを使用した.

主要な成果:

大幅な増加 (約. 反応性酵素基板コンフォマー (近攻撃コンフォマー,NAC) で1100倍) が,298Kと比較して385Kで観察されました.
NACの集団は,より高い温度で観察された反応速度の増加と直接相関していた.
活性部位残留物であるLys53とLys110は,触媒の基質の方向化に決定的に重要であると特定されました.

結論:

温度に依存するNACの増加は,IGPSにおける一般的な酸性触媒を促進します.
NACの形成は,反応の自由エネルギーの温度依存に大きく寄与する.

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