Mechanism for enzyme-catalyzed reactions: Small molecule model reactions; structure-reactivity studies on mutant enzymes; the role of flexible loops; and, mechanisms for transition-state stabilization
Buffalo NY, 14260
Phone: (716) 645-4232
Fax: (716) 645-6963
Mechanisms of enzyme-catalyzed reactions and the reactions of small molecules in solution that may be models for enzyme catalysis.
The field of molecular biology requires a community of biologists who possess an intuitive understanding of how to delineate the many complex cellular and higher-order processes which occur in living systems, and of chemists and biochemists who possess the ability to determine the underlying chemical mechanism for these biological processes. Within the latter community studies of enzymes and their reaction mechanisms have long provided a unique understanding of how life functions at a molecular level.
There are many questions that can be raised about the mechanism for uncatalyzed and enzyme-catalyzed reactions of small molecules in water. What are the lifetimes of carbanion and carbenium ion intermediates of these reactions, and how does their lifetime govern the reaction mechanism? Why are some reaction mechanisms stepwise and other mechanisms concerted? What imperatives determine the chemical mechanisms for enzyme-catalyzed reactions? What is the origin of the rate acceleration for enzymatic reactions. What are the intermediates of enzyme-catalyzed reactions, and how are these species stabilized by interaction with the protein catalyst?
Research projects in progress at this time in Professor Richard’s lab include: (1) The determination of the rate and equilibrium constants for addition of nucleophilic reagents to simple carbenium ions and the effect of changing carbenium ion structure on these kinetic and thermodynamic parameters. (2) The generation of biologically important enolates, and development of experimental protocol to estimate the pKas for weak carbon acids. (3) Studies on the mechanism for nonenzymatic and enzyme-catalyzed aldol addition reactions in water. (4) The determination of the mechanistic imperatives for nonenzymatic and enzyme-catalyzed aldose-ketose and allylic isomerization reactions. (5) The characterization of the transition state and intermediates of b-galactosidase catalyzed hydrolysis of glycosides and determination of the function of essential amino-acid residues in the enzymatic reaction.