期刊
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
卷 7, 期 8, 页码 2610-2616出版社
AMER CHEMICAL SOC
DOI: 10.1021/ct200129q
关键词
-
资金
- Scientific Grant Agency of the Ministry of Education of Slovak Republic
- Slovak Academy of Sciences [VEGA-02/0176/09]
- Slovak Research and Development Agency [APVV-0117-06]
- Austrian Federal Ministry of Science and Research (Action Austria-Slovakia) [ICM-2010-02933]
- European Community [FP7/2007-2013, 212043]
The first reaction step of the redox cycle of bovine erythrocyte glutathione peroxidase from class 1 (GPX1) was investigated using hybrid quantum mechanics/molecular mechanics (QM/MM) calculations using the ONIOM methodology. The reduction of hydrogen peroxide by the active-site selenocysteine in selenolate form assisted by the Arg177 residue was modeled based on a proposal from previous molecular dynamics simulations and pK(a) calculations (J. Chem. Theory Comput. 2010, 6, 1670-1681). The redox reaction is predicted as a concerted S(N)2 nucleophilic substitution with a concomitant proton transfer from Arg177 onto leaving hydroxide ion upon reduction of hydrogen peroxide. The height of the reaction barrier was predicted in range of 6-11 kcal mol(-1), consistent with an experimental rate constant of ca. 10(7) M(-1) s(-1). The proposed GPX1-Se(-)-Arg177H(+) mechanism for GPX1 is compared with the GPX3-SeH-Gln83 one proposed for human glutathione peroxidase from class 3 (GPX3) and with the solvent-assisted proton exchange mechanism proposed for GPX-like organic selenols. The structural and energetic parameters predicted by various density functional theory methods (B3LYP, MPW1PW91, MPW1K, BB1K, M05-2X, M06-2X, and M06) are also discussed.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据