Protein hydration changes during catalysis: a new mechanism of enzymic rate-enhancement and ion activation/inhibition of catalysis.

There exists a linear correlation between the effect of a salt on the rate of an enzymic reaction and its effect on the activation volume (delta V++) of the reaction. Salts that increase delta V++ invariably decrease the rate of the reaction, and vice versa. The salt effects on reaction rate are, however, much larger than would be predicted solely on the basis of pressure-volume work changes deriving from the observed alterations in delta V++. Different inorganic salts affect reaction rates and activation volumes in a manner that reflects the salts' positions in the Hofmeister series. These observations, taken in conjunction with data on the effects of salts on protein functional group (aminoacid side-chains and peptide linkages) hydration, lead us to propose the following hypothesis to account for salt activation and inhibition of catalysis. Aminoacid side-chains and peptide linkages located on or near the protein surface change their exposure to water during conformational events in catalysis. These protein group transfers are accompanied by large volume and energy changes that are due largely to changes in the organization of water around these groups. When these transfer processes occur during the rate-limiting step in catalysis, these energy and volume changes can contribute to the free energy of activation (delta G++) and the activation volume of the reaction. By influencing the degree to which water can organize around transferred protein groups, salts can modify both the delta G++ (rate) and the delta V++ of a reaction.