engleski

Coenzyme B12-Dependent Fermentation of Glycerol - A Computational Study

Some bacteria are able to grow under anaerobic conditions using alcohols such as diols and glycerol as the primary source of carbon.1, 2 The first step of this process is catalyzed by specific dehydratase enzymes whose action is dependent on coenzyme B12. In order to better understand these important processes, we have investigated the radical-based mechanism of dehydration of glycerol catalyzed by the coenzyme B12-dependent enzyme glycerol dehydratase (EC 4.2.1.30) using combination of classical, quantum and hybrid quantum mechanic/molecular mechanic (QM/MM) methods. Initially, the enzyme-substrate complex was appropriately parameterized, minimized and then equilibrated for 2 ns in an NVT molecular dynamics simulation. A QM/MM region consisting of 2180 atoms was then chosen from the best average structure from the MD simulation. From here, three steps of dehydration process, namely, the initial and final hydrogen abstraction and hydroxyl group migration, were characterized in the QM/MM environment with electrostatic embedding. Kinetic isotope effects including tunnelling corrections are calculated for the hydrogen transfer steps, and potential pathways for the OH group migration are identified.

QM/MM; B12-dependent enzymatic fermentation; glycerol dehydratase

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