ABSTRACT
The B12s, also referred to as cobalamin coenzymes, are complex macrocycles whose reactivity is associated with a unique cobaltcarbon bond. The structures of two cobalamin-dependent enzymes, methionine synthase and methylmalonyl-CoA mutase, have been solved. In both cases the cobalt is coordinated by a histidine ligand from the protein. The significance of this binding motif is presently unclear since in other cobalamin-dependent enzymes spectroscopic evidence suggests that the coenzyme’s nucleotide ‘tail’ remains coordinated to cobalt when bound to the protein. Methionine synthase from Escherichia coli is the most further studied B12-dependent enzyme. One of the better-understood systems is the methanobacterium thermoautotrophicum methyltransferase, which catalyses the transfer of a methyl group from methyltetrahydromethanopterin to mercaptoethane sulphonate, a reaction chemically very similar to that catalysed by methionine synthase. Hydroxocobalamin was used as an antidote in experimental cyanide poisoning in mice in 1952 and has since been shown to be efficacious in a variety of animal models.
