Document Type




Format of Original

2 p.

Publication Date



American Chemical Society

Source Publication

Journal of the American Chemical Society

Source ISSN


Original Item ID

DOI: 10.1021/ja061435a


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.


Accepted version. Journal of the American Chemical Society, Vol. 128, No. 24 (May 2006): 7724-7725. DOI. © 2006 American Chemical Society. Used with permission.

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