Isothermal compressibility of macromolecular crystals and macromolecules derived from high‐pressure X‐ray crystallography

The compressibility of several nucleic acid and globular protein crystals has been investigated by high-pressure macromolecular crystallography. Further, crystal structures at four different pressures allowed the determination of the intrinsic compressibility versus pressure of d(GGTATACC)2 and hen egg-white lysozyme. For lysozyme, the values for the intrinsic molecular compressibility at atmospheric pressure and the nonlinearity index were 0.070 GPa−1 and 8.15, respectively. On the basis of two crystal structures at atmospheric and high pressure, similar, albeit less complete, information was derived for d(CGCGAATTCGCG)2 and bovine erythrocyte Cu,Zn superoxide dismutase. Using these data and accurate calculations of the solvent-excluded volume, the apparent solvent compressibility in the crystalline state was determined as a function of pressure and compared with results from a simple model that assumes invariant unit-cell content, with the conclusion that solvent compressibility was abnormal for three out of the five crystals investigated. Experimental results suggest that macromolecular crystals submitted to high pressure may have a variable unit-cell mass due to solvent exchange with the surrounding pool, as already observed in other hydrated crystals such as zeolites.