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Water is thought of as the universal solvent for biological macromolecules, and its interaction with the different amino acid side chains of proteins determines their folding. Only a small proportion of the water associated with enzymes is tightly bound, but this can play crucial roles in determining the rates and specificities of reactions. Water itself is a relatively poor nucleophile, and enzymes can employ different strategies to facilitate hydrolytic reactions.

Enzyme action: lock up your waters?: Water and active sites