Engineering of Antibodies with a Known Three-dimensional Structure

Abstract

There are several approaches to the study of catalysis. Most paradigms of enzymology are the fruit of the first approach, the continuous search for new enzymes and their judicious study. This "discovery" approach has led not only to the characterization of enzymes catalyzing new reaction types, but also to the meticulous dissection of the simplest elementary catalytic steps. A second approach, the modification of one enzyme by chemical or, nowadays, mainly genetic means (i.e., the perturbation of the catalytic machinery), has recently also begun to provide further insight into the mechanisms of catalysis (for review, see Leatherbarrow and Fersht 1986; Wetzel 1986; Knowles 1987). Most enzymes have probably evolved to a rather high efficiency. The consequence is that modification will, most probably, only reduce their activity or leave it unaffected when they are tested for the reaction and conditions for which they were intended by nature (Albery and Knowles 1977)....