CONTRIBUTION OF WATER-MOLECULES IN THE INTERIOR OF A PROTEIN TO THE CONFORMATIONAL STABILITY

Water molecules frequently occur in the interior of globular proteins. To elucidate the contribution of buried water molecules to the confor mational stability of a protein, we examined the crystal structures an d the thermodynamic parameters of denaturation of six Ile to Ala/Gly m utant human lysozymes, in which a cavity is created at each mutation s ite by the substitution of a smaller side-chain for a larger one. One or two ordered water molecules were found in the cavities created in s ome mutants (I106A, I59A and I59G). The cavity volumes for these three mutants were bigger than those that remained empty in the other mutan ts. The stability of the mutant proteins with the newly introduced wat er molecules was about 8 kJ/mol higher than that expected from the cha nge in hydrophobic surface area (Delta Delta ASA(HP)) exposed upon den aturation. It was concluded that a water molecule in a cavity created in the interior of a protein contributes favorably to the stability. ( C) 1997 Academic Press Limited.