Experimental Evidence and Mechanistic Description of the Phenolic H-Transfer to the Cu2O2 Active Site of oxy-Tyrosinase

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388955%3A_____%2F23%3A00576720" target="_blank" >RIV/61388955:_____/23:00576720 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388963:_____/23:00576720 RIV/00216208:11310/23:10478596

Výsledek na webu

<a href="https://doi.org/10.1021/jacs.3c07450" target="_blank" >https://doi.org/10.1021/jacs.3c07450</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/jacs.3c07450" target="_blank" >10.1021/jacs.3c07450</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Experimental Evidence and Mechanistic Description of the Phenolic H-Transfer to the Cu2O2 Active Site of oxy-Tyrosinase

Popis výsledku v původním jazyce

Tyrosinase is a ubiquitous coupled binuclear copper enzyme that activates O2 toward 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 Cu2O2 core 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 Cu2O2 active sites in biology.

Název v anglickém jazyce

Experimental Evidence and Mechanistic Description of the Phenolic H-Transfer to the Cu2O2 Active Site of oxy-Tyrosinase

Popis výsledku anglicky

Tyrosinase is a ubiquitous coupled binuclear copper enzyme that activates O2 toward 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 Cu2O2 core 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 Cu2O2 active sites in biology.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

<a href="/cs/project/GA23-05940S" target="_blank" >GA23-05940S: Katalytické metalopeptidy coby propojení světa nízkomolekulárních katalyzátorů a metaloenzymů</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of the American Chemical Society

ISSN

0002-7863

e-ISSN

1520-5126

Svazek periodika

145

Číslo periodika v rámci svazku

42

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

5

Strana od-do

22866-22870

Kód UT WoS článku

001140769100001

EID výsledku v databázi Scopus

2-s2.0-85175269664