The goal of this research is to understand how the amino acid sequence of an enzyme encodes its three-dimensional structure, and how this structure manifests itself in function.Enzyme function and protein structure are both manifestations of molecular recognition. The PI is using the tools of chemistry, biochemistry, and molecular biology to determine how molecular recognition leads to enzyme action. The research concentrates on two facets of molecular recognition: enzyme-substrate recognition (that is, enzymatic catalysis) and intramolecular protein-protein recognition (that is, protein folding). Dr. Reines is focusing on catalysis by and folding of ribonuclease A (RNase A). By analyzing in detail the structure and function of mutant RNase A's, they are delineating the contribution of particular amino acid residues to substrate recognition and turnover and to protein folding. They are also interested in protein disulfide isomerase (PDI), which catalyzes the interchange of disulfide bonds in other proteins. They have cloned the cDNA that codes for PDI, and are attempting to express it in yeast. The goal is to illuminate the mechanism of catalysis by PDI. A considerable effort is being made to develop efficient, selective catalysts for the synthesis and degradation of complex molecules. Much inspiration for this effort has come from the study of nature's catalysts, the enzymes. Illuminating the molecular interactions that give rise to substrate binding and turnover may provide the knowledge necessary to design a protein structure that catalyzes a specific chemical reaction. This knowledge, together with the ability to specify a sequence of amino acids that folds into a desired three-dimensional structure, would allow protein engineers to create novel catalysts for medicinal analyses and therapies, and for industrial processes.
