Department of Chemistry, University of Louisville, Louisville, KY 40292, United States.
Department of Theoretical Chemistry, Institute of Chemistry, University of Silesia in Katowice, Szkolna 9, PL-40 006 Katowice, Poland.
J Photochem Photobiol B. 2018 Dec;189:306-317. doi: 10.1016/j.jphotobiol.2018.09.015. Epub 2018 Sep 20.
Methylcobalamin (MeCbl)-dependent enzyme methionine synthase (MetH), plays a critical role in the catalysis of methyl group transfer from methyltetrahydrofolate (CH-Hfolate) to homocysteine. It often performs a side reaction to generate cob(II)alamin through photolysis of the organometallic CoC σ bond. A hybrid QM/MM method has been applied to explore the photochemistry of MeCbl-bound MetH. The photolytic properties of MeCbl inside MetH are mediated by its manifold of low-lying excited states. The corresponding potential energy surfaces (PESs) of the electronically excited S state has been constructed as a function of axial bond lengths to elucidate the mechanism of photo-induced activation of CoC bond inside the enzyme. The analysis of the S PES has revealed that the two different electronic states of the S PES, namely metal-to-ligand charge transfer (MLCT) and the ligand field (LF), are relevant to the photodissociation of the CoC bond. There are two possible pathways identified, Path A and Path B, that connect the MLCT to LF state that represent possible photodissociation mechanisms. In the case of MetH, one possible photodissociation pathway (Path B) was identified based on the energetics of the MLCT and LF states. The energetically accessible Path B involves the initial detachment of the Co-N bond followed by a subsequent displacement of the CoC bond prior to the formation of cob(II)alamin / CH radical pair (RP). The photochemical data of base-on MeCbl in solution was compared with the computed result of MeCbl-bound MetH to understand the effect of the enzymatic environment on the photolytic properties of MeCbl.
甲钴胺（MeCbl）依赖性酶蛋氨酸合酶（MetH）在催化从甲基四氢叶酸（CH-Hfolate）向同型半胱氨酸转移甲基基团中起着关键作用。它通常通过有机金属 CoC σ 键的光解进行副反应，生成 cob(II)alamin。已经应用混合 QM/MM 方法来探索 MeCbl 结合的 MetH 的光化学。MeCbl 在 MetH 中的光解性质受其多个低能激发态的调节。构建了电子激发 S 态的相应势能面（PES）作为轴向键长的函数，以阐明酶内 CoC 键光诱导活化的机制。S PES 的分析表明，S PES 的两个不同电子态，即金属-配体电荷转移（MLCT）和配体场（LF），与 CoC 键的光解有关。已经确定了两条可能的途径，途径 A 和途径 B，它们将 MLCT 连接到 LF 状态，代表可能的光解机制。在 MetH 的情况下，根据 MLCT 和 LF 状态的能量，确定了一条可能的光解途径（途径 B）。能量上可及的途径 B 涉及 Co-N 键的初始断裂，随后 CoC 键的位移，然后形成 cob(II)alamin / CH 自由基对（RP）。将溶液中基于碱基的 MeCbl 的光化学数据与计算得到的 MeCbl 结合的 MetH 的结果进行比较，以了解酶环境对 MeCbl 光解性质的影响。
