engleski

QM/MM study of the inactivation of the B12-dependent dehydratases by substrate glycerol

Some bacteria use alcohol as a source of carbon and energy in order to grow in anaerobic conditions via fermentation. The fermentation of alcohol starts with the dehydration (Figure 1). This reaction is catalyzed by two enzymes: glycerol dehydratase (GDH) and diol dehydratase (DDH), which use coenzyme B12 as an essential cofactor.[1] As with most B12-dependent reactions, the reaction mechanism of these two enzymes involves a formation of radical intermediates. It is known that both GDH and DDH undergo substrate-induced inactivation by glycerol, the rate of which is higher for DDH than for the GDH.[2] Possible inactivation mechanism is recently reported by Yoshizawa et al. It states that glycerol C1 radical can abstract hydrogen from C3 hydroxyl group forming unstable O-centered radical which undergoes homolytic cleavage to form formaldehyde and glycol radical.[3, 4] In this work we propose and explore another mechanism of inactivation for GDH and DDH that does not require energetically expensive intramolecular hydrogen transfer from hydroxyl group to C1 radical. The energy profiles of the proposed inactivation mechanism for both enzymes yielded activation energies that are more consistent with the experimental data providing better explanation to underlying mechanism for the unusual “suicidal” inactivation of GDH and DDH

B12-dependent dehydratases ; inhibition ; reaction mechanism

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