Crystal structures of the free and liganded form of an esterolytic catalytic antibody

The crystal structure of the esterase catalytic antibody 48G7 has been determined in the presence of hapten at 2.0 Angstrom resolution and in the absence of hapten at 2.7 Angstrom resolution. The root-mean-square difference between the two structures is 0.6 Angstrom for the variable domain and 0.7 Angstrom for the constant domain. Comparison of the active site sl-rows that no signiiicant changes occur upon hapten binding as main-chain and side-chain displacements are negligible. Complex formation occurs as hapten fits into a pre-formed pocket about 10 Angstrom deep. Although 151 water molecules were modeled into the 48G7-hapten structure, none are bound in the active site. Comparison of the 48G7 structures with those of other published ester hydrolysis antibodies illustrates an emerging theme used by esterolytic antibodies in binding their (nitro-)phenyl haptens and in hydrolysing their cognate esters and carbonates: hapten is bound with the aryl end buried deep in the binding pocket, and the phosphonate moiety is responsible for the majority of the binding energy to the antibody-hapten interaction. (C) 1997 Academic Press Limited.