Adenosylcobalamin-dependent isomerases: new insights into structure and mechanism

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.