Catalysis of decarboxylation by a preorganized heterogeneous microenvironment: Crystal structures of abzyme 21D8

Antibody 21D8 catalyzes the solvent-sensitive decarboxylation of 3-carboxyb enzisoxazoles. The crystal structure of chimeric Fab 21D8 with and without hapten at 1.61 Angstrom and 2.10 Angstrom, respectively, together with comp utational analysis, shows how a melange of polar and non-polar sites are ex ploited to achieve both substrate binding and acceleration of a reaction no rmally facilitated by purely aprotic dipolar media. The striking similarity of the decarboxylase and a series of unrelated esterase antibodies also hi ghlights the chemical versatility of structurally conserved anion binding s ites and the relatively subtle changes involved in fine-tuning the immunogl obulin pocket for recognition of different ligands and catalysis of differe nt reactions. (C) 2000 Academic Press.