Elucidation of factors shaping reactivity of 5′-deoxyadenosyl - a prominent organic radical in biology

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388955%3A_____%2F24%3A00588381" target="_blank" >RIV/61388955:_____/24:00588381 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61388963:_____/24:00588381

Výsledek na webu

<a href="https://hdl.handle.net/11104/0355282" target="_blank" >https://hdl.handle.net/11104/0355282</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/d4cp01725k" target="_blank" >10.1039/d4cp01725k</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Elucidation of factors shaping reactivity of 5′-deoxyadenosyl - a prominent organic radical in biology

Popis výsledku v původním jazyce

This study investigates the factors modulating the reactivity of 5´-deoxyadenosyl (5´ dAdo(center dot)) radical, a potent hydrogen atom abstractor that forms in the active sites of radical SAM enzymes and that otherwise undergoes a rapid self-decay in aqueous solution. Here, we compare hydrogen atom abstraction (HAA) reactions between native substrates of radical SAM enzymes and 5´ dAdo(center dot) in aqueous solution and in two enzymatic microenvironments. With that we reveal that HAA efficiency of 5´ dAdo(center dot) is due to (i) the in situ formation of 5´ dAdo(center dot) in a pre-ordered complex with a substrate, which attenuates the unfavorable effect of substrate:5´ dAdo(center dot) complex formation, and (ii) the prevention of the conformational changes associated with self-decay by a tight active-site cavity. The enzymatic cavity, however, does not have a strong effect on the HAA activity of 5´ dAdo(center dot). Thus, we performed an analysis of in-water HAA performed by 5´ dAdo(center dot) based on a three-component thermodynamic model incorporating the diagonal effect of the free energy of reaction, and the off-diagonal effect of asynchronicity and frustration. To this aim, we took advantage of the straightforward relationship between the off-diagonal thermodynamic effects and the electronic-structure descriptor the redistribution of charge between the reactants during the reaction. It allows to access HAA-competent redox and acidobasic properties of 5´ dAdo(center dot) that are otherwise unavailable due to its instability upon one-electron reduction and protonation. The results show that all reactions feature a favourable thermodynamic driving force and tunneling, the latter of which lowers systematically barriers by similar to 2 kcal mol-1. In addition, most of the reactions experience a favourable off-diagonal thermodynamic contribution. In HAA reactions, 5´ dAdo(center dot) acts as a weak oxidant as well as a base, also 5´ dAdo(center dot)-promoted HAA reactions proceed with a quite low degree of asynchronicity of proton and electron transfer. Finally, the study elucidates the crucial and dual role of asynchronicity. It directly lowers the barrier as a part of the off-diagonal thermodynamic contribution, but also indirectly increases the non-thermodynamic part of the barrier by presumably controlling the adiabatic coupling between proton and electron transfer. The latter signals that the reaction proceeds as a hydrogen atom transfer rather than a proton-coupled electron transfer.

Název v anglickém jazyce

Elucidation of factors shaping reactivity of 5′-deoxyadenosyl - a prominent organic radical in biology

Popis výsledku anglicky

This study investigates the factors modulating the reactivity of 5´-deoxyadenosyl (5´ dAdo(center dot)) radical, a potent hydrogen atom abstractor that forms in the active sites of radical SAM enzymes and that otherwise undergoes a rapid self-decay in aqueous solution. Here, we compare hydrogen atom abstraction (HAA) reactions between native substrates of radical SAM enzymes and 5´ dAdo(center dot) in aqueous solution and in two enzymatic microenvironments. With that we reveal that HAA efficiency of 5´ dAdo(center dot) is due to (i) the in situ formation of 5´ dAdo(center dot) in a pre-ordered complex with a substrate, which attenuates the unfavorable effect of substrate:5´ dAdo(center dot) complex formation, and (ii) the prevention of the conformational changes associated with self-decay by a tight active-site cavity. The enzymatic cavity, however, does not have a strong effect on the HAA activity of 5´ dAdo(center dot). Thus, we performed an analysis of in-water HAA performed by 5´ dAdo(center dot) based on a three-component thermodynamic model incorporating the diagonal effect of the free energy of reaction, and the off-diagonal effect of asynchronicity and frustration. To this aim, we took advantage of the straightforward relationship between the off-diagonal thermodynamic effects and the electronic-structure descriptor the redistribution of charge between the reactants during the reaction. It allows to access HAA-competent redox and acidobasic properties of 5´ dAdo(center dot) that are otherwise unavailable due to its instability upon one-electron reduction and protonation. The results show that all reactions feature a favourable thermodynamic driving force and tunneling, the latter of which lowers systematically barriers by similar to 2 kcal mol-1. In addition, most of the reactions experience a favourable off-diagonal thermodynamic contribution. In HAA reactions, 5´ dAdo(center dot) acts as a weak oxidant as well as a base, also 5´ dAdo(center dot)-promoted HAA reactions proceed with a quite low degree of asynchronicity of proton and electron transfer. Finally, the study elucidates the crucial and dual role of asynchronicity. It directly lowers the barrier as a part of the off-diagonal thermodynamic contribution, but also indirectly increases the non-thermodynamic part of the barrier by presumably controlling the adiabatic coupling between proton and electron transfer. The latter signals that the reaction proceeds as a hydrogen atom transfer rather than a proton-coupled electron transfer.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Physical Chemistry Chemical Physics

ISSN

1463-9076

e-ISSN

1463-9084

Svazek periodika

26

Číslo periodika v rámci svazku

30

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

16

Strana od-do

20280-20295

Kód UT WoS článku

001274210600001

EID výsledku v databázi Scopus

2-s2.0-85199403186