Radical carbon skeleton rearrangements:: Catalysis by coenzyme B12-dependent mutases

The availability of relatively large amounts of recombinant protein in the past decade has driven studies on AdoCbl-dependent enzymes to a deeper level of inquiry. Crystal structures of two of the carbon skeleton isomerases reveal similarities in the overall molecular architecture and in the mode of B12 binding but differences in the constellation of active-site residues that probably reflect evolutionary fine-tuning for different catalytic mechanisms. The structure of glutamate mutase has provided unexpected insights into how the cofactor-derived deoxyadenosyl radical shuttles between recombination and substrate (or product) radical generation via a conformational toggle of the ribose ring. Kinetic and mutagenesis studies are beginning to shed light on details of the rearrangement reaction and the roles of individual active-site residues in the remarkable stabilization of radical intermediates and suppression of radical interception by side reactions.