Structures of the methyltransferase component ofDesulfitobacterium hafnienseDCB-2O-demethylase shed light on methyltetrahydrofolate formation

Abstract

O-Demethylation by acetogenic or organohalide-respiring bacteria leads to the formation of methyltetrahydrofolate from aromatic methyl ethers.O-Demethylases, which are cobalamin-dependent, three-component enzyme systems, catalyse methyl-group transfers from aromatic methyl ethers to tetrahydrofolateviamethylcobalamin intermediates. In this study, crystal structures of the tetrahydrofolate-binding methyltransferase module from aDesulfitobacterium hafnienseDCB-2O-demethylase were determined both in complex with tetrahydrofolate and the product methyltetrahydrofolate. While these structures are similar to previously determined methyltransferase structures, the position of key active-site residues is subtly altered. A strictly conserved Asn is displaced to establish a putative proton-transfer network between the substrate N5 and solvent. It is proposed that this supports the efficient catalysis of methyltetrahydrofolate formation, which is necessary for efficientO-demethylation.