Cobalamin-dependent methyltransferases

Cobalamin cofactors play critical roles in radical-catalyzed rearrangements and in methyl transfers. This Account focuses on the role of methylcobalam in and its structural homologues, the methylcorrinoids, as intermediaries i n methyl transfer reactions, and particularly on the reaction catalyzed by cobalamin-dependent methionine synthase. In these methyl transfer reactions , the cobalt(I) form of the cofactor serves as the methyl acceptor. Biologi cal methyl donors to cobalamin include N5-methyltetrahydrofolate, other met hylamines, methanol, aromatic methyl ethers, acetate, and dimethyl sulfide. The challenge for chemists is to determine the enzymatic mechanisms for ac tivation of these unreactive methyl donors and to mimic these amazing biolo gical reactions.