ABSTRACT
In 1946 Linus Pauling first formulated the basic principle underlying enzyme catalysis, namely, that an enzyme increases the rate of a chemical reaction by binding and stabilizing the transition state of its specific substrate tighter than the ground state. However, for many years it was not generally appreciated that the high affinity of an enzyme for the transition state of a substrate plays a major role in determining substrate specificity as well as the rate of catalysis. In the past few years, kinetic studies of site-directed mutants, combined with x-ray structures, have made it possible to identify unambiguously the role of particular amino acids in both the substrate specificity and the catalytic reaction of an enzyme as well as providing information about the energetic basis of catalysis itself. The full consequences of Pauling’s principle emerged only when it was found that mutants designed to change an enzyme’s catalytic rate also changed its substrate specificity and vice versa.
