Resolving Enzyme Mechanisms of Phosphate Transfer

Friday, 26 April 2013 - 1:00pm - 2:00pm
Lecture Hall LECT 105

Westheimer Lecture Series

Frank H. Westheimer (1912 - 2007) was Morris Loeb Professor of Chemistry Emeritus at Harvard University. After his Harvard Ph.D., he trained in Columbia with Louis P Hammett, the father of physical organic chemistry, and also studied physics and electrostatics plus statistical mechanics. Those skills equipped him in Chicago to study isotopes and their uses in organic chemistry and led him into a study of enzyme mechanisms.

A renewed interest in organophosphorus compounds and their reaction mechanisms led into problems related to phosphate processes in biochemistry, especially for adenosine triphosphate and ribonuclease. These called for new experimental techniques and their analysis demanded dramatically new concepts in reactivity, especially related to dynamic stereochemistry.

As an Emeritus Harvard Professor, he became committed to understanding the fundamental role of phosphorus in life and attempted to rationalize it in terms of the breadth of his knowledge of phosphates.  Frank Westheimer is regarded as the Father of Mechanistic Biological Chemistry by many of his successors and followers.

Resolving Enzyme Mechanisms of Phosphate Transfer

Enzyme catalyzed phosphoryl transfer mechanisms lie at the heart of life. I shall illustrate this using the biosynthesis of ATP involving a proton gradient across a membrane, by the polymerisation of RNA using ATP etc., and by energy production from metabolising glucose via 1,3-diphosphoglyceric acid. The strengths and also the shortcomings of analysis of protein structures by crystallography divorced from chemistry will be exemplified. Finally the centrality of studies on transition states to understand mechanisms will be applied to a unified theory of phosphoryl transfer in the isomerisation, hydrolysis, and alcoholysis of phosphate monoesters and anhydrides.


Lynn Gerrard
Department of Chemistry and Chemical Biology