Topology of DNA G-Quadruplexes Can Be Harnessed in Holliday Junction-Based DNA Suprastructures to Control and Optimize Their Biocatalytic Properties

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F23%3A00574950" target="_blank" >RIV/68081707:_____/23:00574950 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15640/23:73621631

Výsledek na webu

<a href="https://pubs.acs.org/doi/10.1021/acscatal.3c02818" target="_blank" >https://pubs.acs.org/doi/10.1021/acscatal.3c02818</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acscatal.3c02818" target="_blank" >10.1021/acscatal.3c02818</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Topology of DNA G-Quadruplexes Can Be Harnessed in Holliday Junction-Based DNA Suprastructures to Control and Optimize Their Biocatalytic Properties

Popis výsledku v původním jazyce

Thenature, composition, and topology of the active sitesof bothnatural and artificial enzymes are key determinants of their catalyticperformance. While interesting structural insights have been obtainedfor natural enzymes (e.g., horseradish peroxidase, HRP), the accuratecatalytic microenvironment of HRP-mimicking DNA-based catalysts knownas G-quadruplex (GQ)/hemin DNAzymes is still unclear. Herein, we reporton a strategy allowing for fully controlling the nature of the activesite of GQ DNAzyme, precisely manipulating the composition and topologyof the hemin (Fe(III)-protoporphyrin IX) cofactor binding site. Thiswas achieved by introducing GQ within a Holliday junction (HJ) suprastructurethat enables to seize control of both the GQ folding topology (parallel,antiparallel, hybrid) and the GQ strand directionality (clockwise,counter-clockwise). By doing so, we demonstrate that the differentGQ topologies are equivalent for both hemin binding and activationand that the flanking nucleotides (dA or dTC) modulate the activationof hemin in a GQ topology-dependent manner. Our experimental findingsare supported by the most extensive molecular dynamics simulationsever been done on GQ DNAzyme, thus providing unique mechanistic insightsinto the biocatalytic activity of GQs.

Název v anglickém jazyce

Topology of DNA G-Quadruplexes Can Be Harnessed in Holliday Junction-Based DNA Suprastructures to Control and Optimize Their Biocatalytic Properties

Popis výsledku anglicky

Thenature, composition, and topology of the active sitesof bothnatural and artificial enzymes are key determinants of their catalyticperformance. While interesting structural insights have been obtainedfor natural enzymes (e.g., horseradish peroxidase, HRP), the accuratecatalytic microenvironment of HRP-mimicking DNA-based catalysts knownas G-quadruplex (GQ)/hemin DNAzymes is still unclear. Herein, we reporton a strategy allowing for fully controlling the nature of the activesite of GQ DNAzyme, precisely manipulating the composition and topologyof the hemin (Fe(III)-protoporphyrin IX) cofactor binding site. Thiswas achieved by introducing GQ within a Holliday junction (HJ) suprastructurethat enables to seize control of both the GQ folding topology (parallel,antiparallel, hybrid) and the GQ strand directionality (clockwise,counter-clockwise). By doing so, we demonstrate that the differentGQ topologies are equivalent for both hemin binding and activationand that the flanking nucleotides (dA or dTC) modulate the activationof hemin in a GQ topology-dependent manner. Our experimental findingsare supported by the most extensive molecular dynamics simulationsever been done on GQ DNAzyme, thus providing unique mechanistic insightsinto the biocatalytic activity of GQs.

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

2023

Kód důvěrnosti údajů

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

Název periodika

ACS Catalysis

ISSN

2155-5435

e-ISSN

2155-5435

Svazek periodika

13

Číslo periodika v rámci svazku

16

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

10722-10733

Kód UT WoS článku

001040999000001

EID výsledku v databázi Scopus

2-s2.0-85167931445