| Autor: |
Kipouros, Ioannis, Stańczak, Agnieszka, Dunietz, Eleanor M., Ginsbach, Jake W., Srnec, Martin, Rulíšek, Lubomír, Solomon, Edward I. |
| Zdroj: |
Journal of the American Chemical Society; October 2023, Vol. 145 Issue: 42 p22866-22870, 5p |
| Abstrakt: |
Tyrosinase is a ubiquitous coupled binuclear copper enzyme that activates O2toward the regioselective monooxygenation of monophenols to catechols via a mechanism that remains only partially defined. Here, we present new mechanistic insights into the initial steps of this monooxygenation reaction by employing a pre-steady-state, stopped-flow kinetics approach that allows for the direct measurement of the monooxygenation rates for a series of para-substituted monophenols by oxy-tyrosinase. The obtained biphasic Hammett plot and the associated solvent kinetic isotope effect values provide direct evidence for an initial H-transfer from the protonated phenolic substrate to the Cu2O2core of oxy-tyrosinase. The correlation of these experimental results to quantum mechanics/molecular mechanics calculations provides a detailed mechanistic description of this H-transfer step. These new mechanistic insights revise and expand our fundamental understanding of Cu2O2active sites in biology. |
| Databáze: |
Supplemental Index |
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