Promiscuity in antibody catalysis: Esterolytic activity of the decarboxylase 21D8

The high structural similarity of decarboxylase antibody 21D8 and esterase antibody 48G7 suggests that 21D8 might also possess hydrolytic activity. Kinetic investigations show that 21138 does promote the selective hydrolysis of methyl 4-nitrophenyl carbonate and sodium 4-(acetoxy)benzenesulfonate with catalytic proficiencies (k(cat)/K-m)/k(un) of ca. 10(5)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.