Our research is directed towards the study of the structural basis of enzyme action through a detailed correlation of the electronic structure, stereochemistry, and molecular structure of enzyme-substrate complexes. In these studies we have developed methods to stabilize catalytically active inte...
Our research is directed towards the study of the structural basis of enzyme action through a detailed correlation of the electronic structure, stereochemistry, and molecular structure of enzyme-substrate complexes. In these studies we have developed methods to stabilize catalytically active intermediates of enzyme reactions with use of organic-aqueous cosolvent mixtures at sub-zero temperatures for structural characterization by magnetic resonance methods. This information provides a picture of the structural basis of interactions between the substrate and enzyme that lead to catalysis. To further understand the structural basis of enzyme action, the interactions of the substrate with active site residues structurally defined through measurement of critical interatomic distances using magnetic resonance methods are analyzed with use of computer controlled molecular graphics and correlated with results of kinetic, chemical, and mutagenic experiments. We have also begun a combined spectroscopic and cell biological investigation into the molecular basis and target enzymes of the insulin-like activity of organic chelates of the vanadyl ion in the insulin signaling pathway.