Jeremy R. Knowles, 1935-2008, in memoriam

It is with great regret that we note the passing of our friend and colleague, Professor Jeremy Knowles, on April 3, 2008. His Memorial Service will be held on Friday, May 30th at 11 am in Memorial Church, Harvard Yard. In lieu of flowers, please consider making a contribution to the charity of your choice. For additional information, please visit www.news.harvard.edu/gazette/2008/04.03/99-knowles.html

Professor Knowles’ research has involved the use of chemical methods and approaches to the solution of biochemical problems. His work has concerned the rate and specificity of enzyme catalysis and the evolution of protein function. He has explored the physical-organic basis for the extraordinary specificity and formidable rates of enzyme-catalyzed reactions, the evolution of enzyme function, the isolation and characterization of enzyme:substrate reaction intermediates, and the stereochemical course of enzyme reactions.

The Knowles group was the first to establish the complete free-energy profile (that is, the full kinetic description) for a simple enzyme-catalyzed reaction, that of triosephosphate isomerase. Since then, many enzymes have been shown to be the most efficient catalysts for their specific reactions, which has given rise to the concept of catalytic perfection. Other contributions have included the use of chiral [16O, 17O, 18O]-phospate esters to probe the nature of enzyme-catalyzed phospho group transfer; the development of photo-affinity labeling by the use of aryl azides; the elucidation of the mechanism of the ß-lactamase inactivator clavulanic acid; and the directed ‘evolution’ of protein function by random mutagenesis and selection. [see also D. E. Hansen, in Bioorg. Chem. 23, 303 (1995)].