Format of Original
American Chemical Society
Journal of the American Chemical Society
Original Item ID
Through characterization of the solvent isotope effect on protein dynamics, we have examined determinants of the rate limitation to enzyme catalysis. A global conformational change in Ribonuclease A limits the overall rate of catalytic turnover. Here we show that this motion is sensitive to solvent deuterium content; the isotope effect is 2.2, a value equivalent to the isotope effect on the catalytic rate constant. We further demonstrate that the protein motion possesses a linear proton inventory plot, indicating that a single proton is transferred in the transition state. These results provide compelling evidence for close coupling between enzyme dynamics and function and demonstrate that characterization of the transition state for protein motion in atomic detail is experimentally accessible.
Kovriguine, Evgueni and Loria, J. Patrick, "Characterization of the Transition State of Functional Enzyme Dynamics" (2006). Chemistry Faculty Research and Publications. 234.
Accepted version. Journal of the American Chemical Society, Vol. 128, No. 24 (May 2006): 7724-7725. DOI. © 2006 American Chemical Society. Used with permission.