Mathematical Models for Enzyme Reactivity: A Case Study in Xanthine Oxidase

Charles (Russ) Hille
Department of Biochemistry, University of California, Riverside

(November 7, 2011 2:30 PM - 3:30 PM)

Mathematical Models for Enzyme Reactivity: A Case Study in Xanthine Oxidase

Abstract

The development of mathematical models for chemical systems based on, for example, density functional theory, have provided key insight into the manner in which chemical transformations occur and the nature of intermediates that form in the course of the reaction. In enzymology, these approaches have proven very successful not only in establishing the chemical sequence of events involved in converting substrate to product but, importantly, how the enzyme accomplishes its critical task physiologically of making the reaction go so fast - typically 1012 to 1014 times faster than the uncatalyzed reaction. Here we dissect the reaction mechanism of the enzyme xanthine oxidase using the tools of density functional theory, and examine the basis for rate acceleration in the context of the enzyme's structure.