STRUCTURAL STUDIES OF CATALYTIC ANTIBODIES

A panel of catalytic antibodies which catalyze ester hydrolysis, trans esterification, porphyrin metallation, Diels-Alder, and redox reaction s has been selected for crystallographic study. While these examples a re 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 ca talysis and strategies for generating catalytic antibodies. However, i t is clear that further progress in the field will benefit greatly fro m 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, electrophi lic catalysis, and transition-state stabilization to be evaluated. Ant ibody and enzyme active sites have been shown to share considerable st ructural and mechanistic similarity, and ongoing structure-function st udies of catalytic antibodies may enhance our understanding of the mec hanisms and evolution of enzymatic catalysis. Structural studies of an tibodies which perform a biological or highly selective reactions shou ld enhance our ability to generate catalysts for important synthetic a pplications. Finally, the combination of high-resolution crystallograp hic analysis with rational mutagenesis should provide a basis for engi neering antibodies with enhanced properties.