Interconversion of (<i>S</i>)-Glutamate and (2<i>S</i>,3<i>S</i>)-3-Methylaspartate:  A Distinctive B<sub>12</sub>-Dependent Carbon-Skeleton Rearrangement WetmoreStacey D. SmithDavid M. GoldingBernard T. RadomLeo 2001 The interconversion of (<i>S</i>)-glutamate and (2<i>S</i>,3<i>S</i>)-3-methylaspartate catalyzed by B<sub>12</sub>-dependent glutamate mutase is discussed using results from high-level ab initio molecular orbital calculations. Evidence is presented regarding the possible role of coenzyme-B<sub>12</sub> in substrate activation and product formation via radical generation. Calculated electron paramagnetic resonance parameters support experimental evidence for the involvement of substrate-derived radicals and will hopefully aid the future detection of other important radical intermediates. The height of the rearrangement barrier for a fragmentation−recombination pathway, calculated with a model that includes neutral amino and carboxylic acid substituents in the migrating glycyl group, supports recent experimental evidence for the interconversion of (<i>S</i>)-glutamate and (2<i>S</i>,3<i>S</i>)-3-methylaspartate through such a pathway. Our calculations suggest that the enzyme may facilitate the rearrangement of (<i>S</i>)-glutamate through (partial) proton-transfer processes that control the protonation state of substituents in the migrating group.