Adenosylcobalamin-dependent isomerases catalyze a variety of chemically dif
ficult 1,2-rearrangements that proceed through a mechanism involving free r
adical intermediates. These radicals are initially generated by homolysis o
f the cobalt-carbon bond of the coenzyme. Recently, the crystal structures
of several of these enzymes have been solved, revealing two modes of coenzy
me binding and highlighting the role of the protein in controlling the rear
rangement of reactive substrate radical intermediates. Complementary data f
rom kinetic, spectroscopic and theoretical studies have produced insights i
nto the mechanism by which substrate radicals are generated at the active s
ite, and the pathways by which they rearrange.