Abstract

Life can be tough – fortunately, we have enzymes that actuate some of the most challenging chemical processes known with great speed and specificity. Though there is an abundance of structural, biochemical, and spectroscopic data on several model enzyme systems, it has remained challenging to identify unifying physical principles that explain the origins of enzymes’ prodigious catalytic powers. Vibrational Stark spectroscopy, a somewhat new addition to the biophysical cannon, is a method we developed that enables one to measure electric fields inside proteins. Using this approach, we found that the active site of ketosteroid isomerase focuses an extremely large electric field onto the bond that breaks in the enzyme’s rate-determining step; moreover, we found that this electric field explains (quantitatively) a substantial portion of this enzyme’s catalytic effect. I believe that the electric field picture that emerges from these results can provide a unifying framework for understanding how enzymes works, and will discuss several implications for future research in enzyme design.