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On the Metal-Aided Catalytic Mechanism for Phosphodiester Bond Cleavage Performed by Nanozymes

[Image: see text] Recent studies have shown that gold nanoparticles (AuNPs) functionalized with Zn(II) complexes can cleave phosphate esters and nucleic acids. Remarkably, such synthetic nanonucleases appear to catalyze metal (Zn)-aided hydrolytic reactions of nucleic acids similar to metallonucleas...

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Autores principales: Pecina, Adam, Rosa-Gastaldo, Daniele, Riccardi, Laura, Franco-Ulloa, Sebastian, Milan, Emil, Scrimin, Paolo, Mancin, Fabrizio, De Vivo, Marco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397296/
https://www.ncbi.nlm.nih.gov/pubmed/34476110
http://dx.doi.org/10.1021/acscatal.1c01215
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author Pecina, Adam
Rosa-Gastaldo, Daniele
Riccardi, Laura
Franco-Ulloa, Sebastian
Milan, Emil
Scrimin, Paolo
Mancin, Fabrizio
De Vivo, Marco
author_facet Pecina, Adam
Rosa-Gastaldo, Daniele
Riccardi, Laura
Franco-Ulloa, Sebastian
Milan, Emil
Scrimin, Paolo
Mancin, Fabrizio
De Vivo, Marco
author_sort Pecina, Adam
collection PubMed
description [Image: see text] Recent studies have shown that gold nanoparticles (AuNPs) functionalized with Zn(II) complexes can cleave phosphate esters and nucleic acids. Remarkably, such synthetic nanonucleases appear to catalyze metal (Zn)-aided hydrolytic reactions of nucleic acids similar to metallonuclease enzymes. To clarify the reaction mechanism of these nanocatalysts, here we have comparatively analyzed two nanonucleases with a >10-fold difference in the catalytic efficiency for the hydrolysis of the 2-hydroxypropyl-4-nitrophenylphosphate (HPNP, a typical RNA model substrate). We have used microsecond-long atomistic simulations, integrated with NMR experiments, to investigate the structure and dynamics of the outer coating monolayer of these nanoparticles, either alone or in complex with HPNP, in solution. We show that the most efficient one is characterized by coating ligands that promote a well-organized monolayer structure, with the formation of solvated bimetallic catalytic sites. Importantly, we have found that these nanoparticles can mimic two-metal-ion enzymes for nucleic acid processing, with Zn ions that promote HPNP binding at the reaction center. Thus, the two-metal-ion-aided hydrolytic strategy of such nanonucleases helps in explaining their catalytic efficiency for substrate hydrolysis, in accordance with the experimental evidence. These mechanistic insights reinforce the parallelism between such functionalized AuNPs and proteins toward the rational design of more efficient catalysts.
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spelling pubmed-83972962021-08-31 On the Metal-Aided Catalytic Mechanism for Phosphodiester Bond Cleavage Performed by Nanozymes Pecina, Adam Rosa-Gastaldo, Daniele Riccardi, Laura Franco-Ulloa, Sebastian Milan, Emil Scrimin, Paolo Mancin, Fabrizio De Vivo, Marco ACS Catal [Image: see text] Recent studies have shown that gold nanoparticles (AuNPs) functionalized with Zn(II) complexes can cleave phosphate esters and nucleic acids. Remarkably, such synthetic nanonucleases appear to catalyze metal (Zn)-aided hydrolytic reactions of nucleic acids similar to metallonuclease enzymes. To clarify the reaction mechanism of these nanocatalysts, here we have comparatively analyzed two nanonucleases with a >10-fold difference in the catalytic efficiency for the hydrolysis of the 2-hydroxypropyl-4-nitrophenylphosphate (HPNP, a typical RNA model substrate). We have used microsecond-long atomistic simulations, integrated with NMR experiments, to investigate the structure and dynamics of the outer coating monolayer of these nanoparticles, either alone or in complex with HPNP, in solution. We show that the most efficient one is characterized by coating ligands that promote a well-organized monolayer structure, with the formation of solvated bimetallic catalytic sites. Importantly, we have found that these nanoparticles can mimic two-metal-ion enzymes for nucleic acid processing, with Zn ions that promote HPNP binding at the reaction center. Thus, the two-metal-ion-aided hydrolytic strategy of such nanonucleases helps in explaining their catalytic efficiency for substrate hydrolysis, in accordance with the experimental evidence. These mechanistic insights reinforce the parallelism between such functionalized AuNPs and proteins toward the rational design of more efficient catalysts. American Chemical Society 2021-07-02 2021-07-16 /pmc/articles/PMC8397296/ /pubmed/34476110 http://dx.doi.org/10.1021/acscatal.1c01215 Text en © 2021 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Pecina, Adam
Rosa-Gastaldo, Daniele
Riccardi, Laura
Franco-Ulloa, Sebastian
Milan, Emil
Scrimin, Paolo
Mancin, Fabrizio
De Vivo, Marco
On the Metal-Aided Catalytic Mechanism for Phosphodiester Bond Cleavage Performed by Nanozymes
title On the Metal-Aided Catalytic Mechanism for Phosphodiester Bond Cleavage Performed by Nanozymes
title_full On the Metal-Aided Catalytic Mechanism for Phosphodiester Bond Cleavage Performed by Nanozymes
title_fullStr On the Metal-Aided Catalytic Mechanism for Phosphodiester Bond Cleavage Performed by Nanozymes
title_full_unstemmed On the Metal-Aided Catalytic Mechanism for Phosphodiester Bond Cleavage Performed by Nanozymes
title_short On the Metal-Aided Catalytic Mechanism for Phosphodiester Bond Cleavage Performed by Nanozymes
title_sort on the metal-aided catalytic mechanism for phosphodiester bond cleavage performed by nanozymes
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397296/
https://www.ncbi.nlm.nih.gov/pubmed/34476110
http://dx.doi.org/10.1021/acscatal.1c01215
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