Conformational Effects on the pro-S Hydrogen Abstraction Reaction in Cyclooxygenase-1: An Integrated QM/MM and MD Study

被引：23

作者：

Christov, Christo Z. ^{[1
,2
]}

Lodola, Alessio ^{[3
]}

Karabencheva-Christova, Tatyana G. ^{[1
,2
]}

Wan, Shunzhou ^{[4
]}

Coveney, Peter V. ^{[4
]}

Mulholland, Adrian J. ^{[1
]}

机构：

[1] Univ Bristol, Sch Chem, Ctr Computat Chem, Bristol, Avon, England

[2] Northumbria Univ, Fac Hlth & Life Sci, Dept Appl Sci, Newcastle Upon Tyne NE1 8ST, Tyne & Wear, England

[3] Univ Parma, Dipartimento Farm, I-43100 Parma, Italy

[4] UCL, Dept Chem, Ctr Computat Sci, London, England

来源：

BIOPHYSICAL JOURNAL | 2013年 / 104卷 / 05期

基金：

英国生物技术与生命科学研究理事会; 英国工程与自然科学研究理事会;

关键词：

ACID AMIDE HYDROLASE; ENZYME CATALYSIS; DYNAMICS; SYNTHASE;

D O I：

10.1016/j.bpj.2013.01.040

中图分类号：

Q6 [生物物理学];

学科分类号：

071011 ;

摘要：

A key step in the cyclooxygenase reaction cycle of cyclooxygenase 1 (COX-1) is abstraction of the pro-S hydrogen atom of the arachidonic acid by a radical that is formed at the protein residue Tyr-385. Here we investigate this reaction step by a quantum-mechanics/molecular-mechanics approach in combination with molecular-dynamics simulations. The simulations identify the hydrogen abstraction angle as a crucial geometric determinant of the reaction, thus revealing the importance of the cyclooxygenase active site for calculating the potential energy surface of the reaction.

引用

页码：L5 / L7

页数：3

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