Solvent entropy contribution to the free energy of protein crystallization

We show with three proteins that trapping and release of the water molecules upon crystallization is a determinant of the crystallization thermodynamics. With HbC, a strong retrograde solubility dependence on temperature yields a high positive enthalpy of 155 kJ mol^-1, i.e., crystallization is only possible because of the huge entropy gain of 610 J mol^-1K^-1, stemming from the release of up to 10 water molecules per protein intermolecular contact. With apoferritin, the enthalpy of crystallization is close to zero. The main component in the crystallization driving force is the entropy gain due to the release upon crystallization of two water molecules bound to one protein molecules in solution. With both proteins, the density of the growth sites imaged by AFM is in excellent agreement with a calculation using the crystallization free energy. With lysozyme, the entropy effect due to the restructuring of the water molecules is negative. This leads to higher solubility.

Structure of mutant human carbonmonoxy­hemoglobin C (βE6K) at 2.0 Å resolution

The first high-resolution crystal structure for liganded hemoglobin C, a mutant hemoglobin that forms crystals in red blood cells of individuals with CC and SC diseases, was obtained from a COHbC crystal grown in concentrated potassium phosphate buffer. The dynamic structure of the βEK6 side chain could potentially support a number of specific polar interactions that may contribute to enhanced nucleation kinetics for HbC relative to HbA.