Evolving understanding of electric fields and enzyme catalysis

Local internal electric fields created by the organized environment in complex systems like proteins can be measured using the vibrational Stark effect (VSE). We have found that these fields can be very large and can affect chemical reactivity. I will briefly explain the underlying physical concept and strategy we have developed to apply the VSE to a wide range of systems. The general concept of electrostatic catalysis and the methods we have developed have proven to be a general approach and have been applied to several enzymes to measure the electrostatic contribution to catalysis. The concept can be extended generally to chemical reactivity, an example being covalent drugs. Recent work addresses the question whether larger fields and correspondingly larger rates can be created either by design or by evolution? Using the hydride transfer enzyme liver alcohol dehydrogenase (LADH), we recently showed that mutations and metal replacements at the active site can produce both larger fields and lower activation free energies (and faster rates), and that these effects are additive, extending and strengthening the concept of electrostatic catalysis. This suggests that an important missing link in the quest for better catalyst design, whether biological or non-biological, may be the electric field.

Speaker: Steven Boxer, Stanford University