Understanding how opposites attract
Proteins are made up of amino acid chains that fold into complex three-dimensional (3D) shapes giving them their unique functionalities and their biological activity. The complex structures of proteins are largely dependent on the positive or negative charges on the individual amino acids. Like charges repel each other and opposites attract. Thus, a detailed understanding of protein charge density leads to a better understanding of the structures of proteins and hence their functions. European researchers supported by funding for the Proteinchargedensity project investigated charge density of the human aldose reductase (h-AR) protein that plays an important role in the side effects of diabetes. h-AR is an enzyme, a protein that acts like a biochemical matchmaker, bringing together two entities attracted to one another but lost in the cell’s milieu and slow to meet on their own. Attraction to the matchmaker is affected by structural and chemical properties, including charge density. Thus, a detailed understanding of charge density of proteins should prove essential to development of therapies for protein-related diseases. The Proteinchargedensity project resulted in refinement of the h-AR protein model and analysis of effects of various factors on charge density. In addition, the investigators evaluated electrostatic interactions of two h-AR inhibitors, given the importance of non-selective binding of inhibitors to other cell molecules interfering with potential therapeutic interventions. The database and unique charge density analysis software created by the laboratory provide important tools for the future study of any given protein’s structure and function. In addition, the specific studies of the h-AR protein’s biochemical and structural characteristics bring us one step closer to new therapies for diabetes, an increasingly prevalent and debilitating disease.