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Analysis of glycerol binding within the active site of B12‐dependent diol dehydratase; implications for catalysis and inhibition

Microbial conversion of crude glycerol, the waste from biofuel production, into compounds of greater industrial value could solve technical difficulties encountered by the conventional means of chemical conversion [1]. During the particular type of microbial conversion, in the first step glycerol undergoes dehydration by enzymes dehydratases into 3‐hydroxylpropionaldehyde (3HPA) [2, 3]. Two classes of dehydratases can catalyze dehydration of glycerol, 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 glycerol, which is their substrate, also acts as an irreversible inhibitor [5]. Based on the B12‐dependent diol dehydratase (B12‐dDDH) crystal structure with glycerol (PDB code: 3AUJ), K. Yoshizawa et al. concluded that the geometry of such bound glycerol enables radical reorganization thus causing inhibition. [6] However, in the recent study on similar enzyme B12‐dependent glycerol dehydratase we observed glycerol in a different geometry [7]. Here we present a detailed computational study of glycerol binding within the active site of B12‐dDDH and find a binding geometry similar to one observed in Ref. 7 (Figure 1). We consider larger 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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