Structural evidence for a programmed general base in the active site of a catalytic antibody

The crystal structure of the complex of a catalytic antibody with its catio nic hapten at 1.9-Angstrom resolution demonstrates that the hapten amidiniu m group is stabilized through an ionic pair interaction with the carboxylat e of a combining-site residue. The location of this carboxylate allows it t o act as a general base in an allylic rearrangement. When compared with str uctures of other antibody complexes in which the positive moiety of the hap ten is stabilized mostly by cation-pi interactions, this structure shows th at the amidinium moiety is a useful candidate to elicit a carboxylate in an antibody combining site at a predetermined location with respect to the ha pten, More generally, this structure highlights the advantage of a bidentat e hapten for the programmed positioning of a chemically reactive residue in an antibody through charge complementarity to the hapten.