Mechanism of the photo-induced activation of CoC bond in methylcobalamin-dependent methionine synthase

Publication date: Available online 20 September 2018

Source: Journal of Photochemistry and Photobiology B: Biology

Author(s): Arghya Pratim Ghosh, Abdullah Al Mamun, Piotr Lodowski, Maria Jaworska, Pawel M. Kozlowski

Abstract

Methylcobalamin (MeCbl)-dependent enzyme methionine synthase (MetH), plays a critical role in the catalysis of methyl group transfer from methyltetrahydrofolate (CH₃-H₄folate) to homocysteine. It often performs a side reaction to generate cob(II)alamin through photolysis of the organometallic CoC 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 S₁ 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 S₁ PES has revealed that the two different electronic states of the S₁ 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_Im bond followed by a subsequent displacement of the CoC bond prior to the formation of cob(II)alamin / CH₃ 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.

Graphical Abstract