The effect of polyethylene glycol on the growth and dissolution rates of a crystalline protein at high salt concentration. Phosphoglucomutase.

Although low concentrations of polyethylene glycol (1-5%, w/v) are essential for growing crystals of phosphoglucomutase from ammonium sulfate solutions (at close to 50% of saturation), the observed rate constant for short-term crystal growth on a defined, microcrystalline surface is essentially independent of polyethylene glycol concentration under these conditions. But this cosolute produces a substantial increase in the observed rate constant for the dissolution process and thus a corresponding increase in the solubility of the crystalline phase. These observations can be rationalized in terms of a decrease in the thermodynamic activity of the soluble form of phosphoglucomutase at high salt due to favorable interactions with polyethylene glycol (PEG) at the protein surface, coupled with a difference in accessibility of protein surfaces in the crystalline and solution states. Surfaces with a differential exposure in these two phases likely include both groups that interact favorably with polyethylene glycol relative to water (nonpolar groups) as well as those that interact unfavorably (ionic groups), but favorable PEG-protein interactions produced on dissolution must outweigh unfavorable ones. A PEG-induced increase in protein solubility at high salt concentration is likely to be general; PEG also may affect the growth of other protein crystals at high salt concentrations as it affects phosphoglucomutase.