Structural Studies of Catalytic Antibodies

A panel of catalytic antibodies which catalyze ester hydrolysis, transesterification, porphyrin metallation, Diels‐Alder, and redox reactions has been selected for crystallographic study. While these examples are only a handful of the catalytic antibodies generated to date, they represent distinct and important aspects of antibody catalysis. Since the first reports of catalysis, a great deal of progress has been made with respect to the scope, selectivity, and efficiency of antibody catalysis and strategies for generating catalytic antibodies. However, it is clear that further progress in the field will benefit greatly from a detailed understanding of the molecular interactions occurring in the combining site. High‐resolution crystallographic data should allow the importance of general base catalysis, entropy effects, electrophilic catalysis, and transition‐state stabilization to be evaluated. Antibody and enzyme active sites have been shown to share considerable structural and mechanistic similarity, and ongoing structure‐function studies of catalytic antibodies may enhance our understanding of the mechanisms and evolution of enzymatic catalysis. Structural studies of antibodies which perform a biological or highly selective reactions should enhance our ability to generate catalysts for important synthetic applications. Finally, the combination of high‐resolution crystallographic analysis with rational mutagenesis should provide a basis for engineering antibodies with enhanced properties.