A view at the millennium: The efficiency of enzymatic catalysis

Binding TS in preference to S and increasing TDeltaS(double dagger) by freezing out motions in E.S and E.TS have been accepted as the driving forces in enzymatic catalysis; however, the smaller value of DeltaG(double dagger) for a one-substrate enzymatic reaction, as compared to its nonenzymatic counterpart, is generally the result of a smaller value of DeltaH(double dagger). Ground-state conformers (E.NACs) are formed in enzymatic reactions that structurally resemble E.TS. E.NACs are in thermal equilibrium with all. other E.S conformers and are turnstiles through which substrate molecules must pass to arrive at the lowest-energy TS. TS in E.TS may or may not be bound tighter than NAC in E.NAC.