Methionine synthase (MetH) enzyme from E. coli is one of the best-studied corrinoid proteins, and it has a modular architecture with four different binding modules. We applied quantum chemical methods (DFT and CASSCF) as well as hybrid QM/MM approaches to understand the mechanistic details of the catalytic methyl transfer reactions. First, we computationally characterized the structure of enzyme-bound cob(I)alamin intermediate using the x-ray structure of the MeCbl binding domain (MetH), because there is no x-ray structure for enzyme-bound cob(I)alamin owing to its high reactivity and supernucleophilic nature. In addition, our QM/MM computations further reveal that cob(I)alamin has a complex electronic structure indicating a non-innocent nature of the corrin ligand. The electronic structure of cob(I)alamin-Im complex was further investigated using a multireference CASSCF calculations to understand the complex nature of this intermediate. The correlated ground state wave function of cob(I)alamin consists of a closed-shell CoI (d8) configuration and a diradical contribution that can be described as CoII (d7)-radical-corrin(p*)1. Based on the electronic structure of cob(I)alamin, we suggested electron transfer (ET)-based radical mechanism as an alternative route for the methyl transfer reaction from CH3-H4Folate to cob(I)alamin complex in addition to traditionally assumed SN2-type pathway.

Mechanistic insight for transmethylation reaction catalyzed by methionine synthase: Quantum-chemical approaches

246th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.