Cardey Bruno, Enescu Mironel
University of Franche-Comte, Laboratoire de Microanalyses Nucleaires, UMR CEA E4, 16 route de Gray, 25030 Besancon, France.
J Phys Chem A. 2007 Feb 1;111(4):673-8. doi: 10.1021/jp0658445.
The cysteine and selenocysteine oxidation by H2O2 in vacuo and in aqueous solution was studied using the integrated molecular orbital + molecular orbital (IMOMO) method combining the quadratic configuration method QCISD(T) and the spin projection of second-order perturbation theory PMP2. It is shown that including in the model system of cysteine (selenocysteine) residue up to 20 atoms has significant consequences upon the calculated reaction energy barrier. On the other hand, it is demonstrated that free cysteine and selenocysteine have very similar reaction energy barriers, 77-79 kJ mol(-1) in aqueous solution. It is thus concluded that the high experimental reaction rate constant reported for the oxidation of the selenocysteine residue in the glutathione peroxidase (GPx) active center is due to an important interaction between selenocysteine and its molecular environment. The sensitivity of the calculated energy barrier to the dielectric constant of the molecular environment observed for both cysteine and selenocysteine as well as the catalytic effect of the NH group emphasized in the case of cysteine supports this hypothesis.
采用结合二次组态相互作用方法QCISD(T)和二阶微扰理论的自旋投影PMP2的集成分子轨道+分子轨道（IMOMO）方法，研究了H2O2在真空和水溶液中对半胱氨酸和硒代半胱氨酸的氧化作用。结果表明，在模型系统中包含多达20个原子的半胱氨酸（硒代半胱氨酸）残基，对计算出的反应能垒有显著影响。另一方面，研究表明游离的半胱氨酸和硒代半胱氨酸具有非常相似的反应能垒，在水溶液中为77 - 79 kJ mol(-1)。因此得出结论，谷胱甘肽过氧化物酶（GPx）活性中心中硒代半胱氨酸残基氧化的高实验反应速率常数，是由于硒代半胱氨酸与其分子环境之间的重要相互作用。对于半胱氨酸和硒代半胱氨酸，计算出的能垒对分子环境介电常数的敏感性，以及在半胱氨酸情况下强调的NH基团的催化作用，都支持了这一假设。
