IMMUNOLOGICAL ORIGINS OF BINDING AND CATALYSIS IN A DIELS-ALDERASE ANTIBODY

The three-dimensional structure of an antibody (39-A11) that catalyzes a Diels-Alder reaction has been determined, The structure suggests th at the antibody catalyzes this pericyclic reaction through a combinati on of packing and hydrogen-bonding interactions that control the relat ive geometries of the bound substrates and electronic distribution in the dienophile. A single somatic mutation, serine-91 of the light chai n to valine, is largely responsible for the increase in affinity and c atalytic activity of the affinity-matured antibody. Structural and fun ctional studies of the germ-line precursor suggest that 39-A11 and rel ated antibodies derive from a family of germ-line genes that have been selected throughout evolution for the ability of the encoded proteins to form a polyspecific combining site. Germ line-encoded antibodies o f this type, which can rapidly evolve into high-affinity receptors for a broad range of structures, may help to expand the binding potential associated with the structural diversity of the primary antibody repe rtoire.