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The high structural similarity of decarboxylase antibody 21D8 and esterase antibody 48G7 suggests that 21D8 might also possess hydrolytic activity. Kinetic investigations show that 21D8 does promote the selective hydrolysis of methyl 4-nitrophenyl carbonate and sodium 4-(acetoxy)benzenesulfonate with catalytic proficiencies (kcat/Km)/kun of ca. 105 M−1. The ability of 21D8 to accelerate a reaction for which it was not developed suggests that certain antibody scaffolds are intrinsically predisposed toward catalysis, a property that can be enhanced and refined during affinity maturation in response to a transition-state analog. At the same time, however, the restricted structural diversity of the immune system may ultimately limit the catalytic efficiency that can be achieved.

Monoclonal antibodies were generated against a 3-phenyl-1,2-benzisoxazole derivative and shown to catalyze the solvent-sensitive decarboxylation of 3-carboxy-1,2-benzisoxazoles. In addition to rate accelerations up to 2300-fold over background, the antibodies exhibit distinctive selectivities for substrates bearing 5- or 6-NO2 substituents, with preferential decarboxylation of the less reactive substrate in one case. These effects are the likely consequence of substrate destabilization, achieved by forcing the carboxylate group into a relatively apolar binding pocket and stabilization of the charge-delocalized transition state through dispersive interactions. Comparison with a more active antibody decarboxylase previously raised against 2-acetamido-naphthalene-1,5-disulfonate suggests, however, that a judicious mix of polar and apolar interactions may ultimately be more effective for achieving high decarboxylase activity.