Conformational Changes during Enzyme Catalysis: Role of Water in the Transition State

The entropy of activation for the synthesis of Ile-tRNA is high and positive. The only likely source of a high Δ S‡is the loss of structured water as the enzyme· substrate complex moves toward the transition state. This requires a change in the orientation or nature of water-organizing residues in the interface between the enzyme· substrate complex and the water. Such changes, which may be some distance from the ``active site,'' are coupled to the active site in such a way that the increased entropy and decreased free energy of the water-enzyme interface is available at the ``active site'' to reduce the free energy of activation. The effects of Hofmeister anions on Kms and kcats are consistent with the entropy data.