Department of Chemistry, University of Louisville, Louisville, KY 40292, USA.
J Biol Inorg Chem. 2012 Apr;17(4):611-9. doi: 10.1007/s00775-012-0881-4. Epub 2012 Feb 23.
Density functional theory has been applied to investigate the methyl transfer from methylcobalamin (MeCbl) cofactor to homocysteine (Hcy) as catalyzed by methionine synthase (MetH). Specifically, the S(N)2 and the reductive elimination pathways have been probed as the possible mechanistic pathways for the methyl transfer reaction. The calculations indicate that the activation barrier for the reductive elimination reaction (24.4 kcal mol(-1)) is almost four times higher than that for the S(N)2 reaction (7.3 kcal mol(-1)). This high energy demand of the reductive elimination pathway is rooted in the structural distortion of the corrin ring that is induced en route to the formation of the triangular transition state. Furthermore, the reductive elimination reaction demands the syn accommodation of the methyl group and the substrate over the upper face of the corrin ring, which also accounts for the high energy demand of the reaction. Consequently, the reductive elimination pathway for MetH-catalyzed methyl transfer from MeCbl to Hcy cannot be considered as one of the possible mechanistic routes.
密度泛函理论已被应用于研究甲硫氨酸合酶（MetH）催化的钴胺素（MeCbl）辅酶与高半胱氨酸（Hcy）之间的甲基转移。具体而言，S(N)2 和还原消除途径已被探测为甲基转移反应的可能机理途径。计算表明，还原消除反应的活化能垒（24.4 kcal mol(-1))）几乎是 S(N)2 反应（7.3 kcal mol(-1))）的四倍。还原消除途径的这种高能量需求源于在形成三角过渡态的过程中诱导的钴胺环的结构变形。此外，还原消除反应需要甲基和底物在钴胺环的上表面上进行顺式容纳，这也导致了反应的高能量需求。因此，MetH 催化的从 MeCbl 到 Hcy 的甲基转移的还原消除途径不能被认为是可能的机理途径之一。
