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

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dc.abstract.enThe nature, composition, and topology of the active sites of both natural and artificial enzymes are key determinants of their catalytic performance. While interesting structural insights have been obtained for natural enzymes (e.g., horseradish peroxidase, HRP), the accurate catalytic microenvironment of HRP-mimicking DNA-based catalysts known as G-quadruplex (GQ)/hemin DNAzymes is still unclear. Herein, we report on a strategy allowing for fully controlling the nature of the active site of GQ DNAzyme, precisely manipulating the composition and topology of the hemin (Fe(III)-protoporphyrin IX) cofactor binding site. This was achieved by introducing GQ within a Holliday junction (HJ) suprastructure that 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 different GQ topologies are equivalent for both hemin binding and activation and that the flanking nucleotides (dA or dTC) modulate the activation of hemin in a GQ topology-dependent manner. Our experimental findings are supported by the most extensive molecular dynamics simulations ever been done on GQ DNAzyme, thus providing unique mechanistic insights into the biocatalytic activity of GQs.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorLanger, Michal
dc.contributor.authorZhou, Jun
dc.contributor.authorMonchaud, David
dc.contributor.authorMergny, Jean-Louis
dc.contributor.authorŠponer, Jiří
dc.contributor.authorJu, Huangxian
dc.contributor.authorGao, Qiang
dc.contributor.authorZhang, Xiaobo
dc.contributor.authorChen, Jielin
dc.contributor.authorStadlbauer, Petr
dc.contributor.authorCheng, Mingpan
dc.contributor.authorQiu, Dehui
dc.date.accessioned2024-01-26T10:54:36Z
dc.date.available2024-01-26T10:54:36Z
dc.date.issued2023
dc.description.financePublikacja bezkosztowa
dc.identifier.doi10.1021/ACSCATAL.3C02818
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/123496
dc.identifier.weblinkhttps://pubs.acs.org/doi/pdf/10.1021/acscatal.3c02818
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofACS Catalysis
dc.relation.pages10722-10733
dc.rightsClosedAccess
dc.sciencecloudnosend
dc.titleTopology of DNA G-Quadruplexes Can Be Harnessed in Holliday Junction-Based DNA Suprastructures to Control and Optimize Their Biocatalytic Properties
dc.typeJournalArticle
dspace.entity.typePublication