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Computational study of glycerol binding within the active site of coenzyme B12-dependent diol dehydratase

Microbial conversion of crude glycerol (GOL), waste from biofuel production, into compounds of greater industrial value could solve technical difficulties encountered by conventional means of chemical conversion [1]. During microbial conversion the first step GOL undergoes is dehydration by enzymes dehydratases into 3-hydroxylpropionaldehyde (3HPA) [2-3]. Two classes of dehydratases can catalyze dehydration of GOL, B12-independent and B12-dependent dehydratases, from which B12- dependent class is more often used due to its tolerance to aerobic conditions [4]. However, a peculiar property of B12-dependent dehydratases is that the substrate GOL also acts as an irreversible inhibitor [5]. Based on the B12- dependent diol dehydratase (B12-dDDH) crystal structure with GOL (PDB code: 3AUJ) K.Yoshizawa et.al. concluded that the geometry of such bound GOL enables radical reorganization causing inhibition [6]. However, in the recent study on similar enzyme B12-dependent glycerol dehydratase employing classical molecular dynamics we observed GOL in a different geometry [7]. Here we present a detailed study of the GOL geometries within the active site of B12-dDDH and consider implications of our findings for the mechanism of substrate induced inactivation.

B12-dependent diol dehydratase ; Substrate binding ; Glycerol inactivation ; Molecular dynamics ; QM/MM calculations

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