Electric Fields and Enzyme Catalysis

We have developed the vibrational Stark effect to probe electrostatics in organized systems, in particular in proteins where vibrational probes can report on functionally important electric fields. The strategy involves deploying site-specific vibrational probes whose sensitivity to an electric field is measured in a calibrated external electric field.  Once calibrated, these probes can be used to probe changes in the electric field due to structural changes.  We can also obtain information on absolute fields by combining vibrational solvatochromism and MD simulations.  This frequency-field calibration is applied to quantify functionally relevant electric fields at the active site of enzymes.  Using ketosteroid isomerase as a model system, we correlate the field sensed at the bond involved in enzymatic catalysis with the rate of the reaction it catalyzes. This provides the first direct connection between electric fields and function: for this system electrostatic interactions are a dominant contribution to catalytic proficiency. 

About the Speaker:
Steven Boxer is the Camille Dreyfus Professor in the Department of Chemistry at Stanford University.  His research interests are in biophysics: the interface of physical chemistry, biology and engineering.  Topics of current interest include: electrostatics and dynamics in proteins, especially related to enzyme catalysis; excited state dynamics of green fluorescent protein, especially split GFP, with applications in biotechnology; electron and energy transfer mechanisms in photosynthesis; and the fabrication of model membranes assemblies to simulate, manipulate and image biological membranes.  He has served on the scientific advisory board of many start-ups in the general area of biotechnology, and as an advisor to government and non-profit organizations in the U.S. and around the world.  He is the recipient of several awards and is an elected Fellow of the American Academy of Arts and Sciences, the Biophysical Society and the National Academy of Sciences.