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

Result code in 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>

Alternative codes found

RIV/61388963:_____/24:00588381

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10403 - Physical chemistry

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

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

Name of the periodical

Physical Chemistry Chemical Physics

ISSN

1463-9076

e-ISSN

1463-9084

Volume of the periodical

26

Issue of the periodical within the volume

30

Country of publishing house

GB - UNITED KINGDOM

Number of pages

16

Pages from-to

20280-20295

UT code for WoS article

001274210600001

EID of the result in the Scopus database

2-s2.0-85199403186