A PERSPECTIVE ON BIOLOGICAL CATALYSIS

We have analysed enzyme catalysis through a re-examination of the reac tion coordinate. The ground state of the enzyme-substrate complex is s hown to be related to the transition state through the mean force acti ng along the reaction path; as such, catalytic strategies cannot be re solved into ground state destabilization versus transition state stabi lization. We compare the role of active-site residues in the chemical step with the analogous role played by solvent molecules in the enviro nment of the noncatalysed reaction. We conclude that enzyme catalysis is significantly enhanced by the ability of the enzyme to preorganize the reaction environment. This complementation of the enzyme to the su bstrate's transition state geometry acts to eliminate the slow compone nts of solvent reorganization required for reactions in aqueous soluti on. Dramatically strong binding of the transition state geometry is no t required.