The molecular mechanisms that mediate evolution and creation of enzyme catalysts are constrained by both protein structure/dynamics and the chemical imperatives of transition state stabilization.Although substantial progress has been made in elucidating the pathways by which enzymes evolve new activities,many questions remain as to the plasticity of protein structures and the extent to which active site residues can be modified in an existing enzyme to yield a functionally different variant.In this lecture,I will discuss the results of (i) recent DFT calculations,(ii) EPR measurements at very high field,and (iii) the kinetic characterization of site-specific mutant enzymes,which have given insight into the electronic structure and reactivity of the metal centers in the Mn-dependent enzymes oxalate oxidase and oxalate decarboxylase[1].