Pii: S0968-0896(98)00247-8

ÐThe theory of absolute reaction rates suggests that enzymes, like other catalysts, can enhance the rate of a reaction only to the extent that they bind the altered substrate in the transition state (S{) more tightly than they bind the substrate in the ground state (S). ES dissociation constants commonly fall in the physiological range, but recent kinetic studies indicate that formal ES{ dissociation constants of less than 10ÿ20M are achieved by enzymes of several classes. Studies with stable analogues suggest that these remarkable powers of discrimination involve a tendency of the enzyme to close around S{ in such a way as to maximize binding contacts; that several parts of the substrate contribute to S{ binding; and that their contributions to binding anity can be strongly synergistic. # 1999 Elsevier Science Ltd. All rights reserved.