Molecular recognition mediated by bound water. A mechanism for star activity of the restriction endonuclease EcoRI.

Many restriction endonucleases such as EcoRI lose some specificity for their recognition sequence under certain buffer conditions. The cause of this disruption of accurate protein-DNA recognition has never been explained. By cleaving DNA with EcoRI in the presence of several osmolytes, we show that the extent of this EcoRI "star activity" depends strongly upon osmotic pressure. The loss of specificity accompanying decreased water activity implies a role for one or more water molecules in recognition of specific sequences of DNA. Water mediation may constitute a general motif for sequence-specific DNA recognition by restriction enzymes and other DNA-binding proteins.