Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1783744583504494592 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8397296 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT pecinaadam onthemetalaidedcatalyticmechanismforphosphodiesterbondcleavageperformedbynanozymes AT rosagastaldodaniele onthemetalaidedcatalyticmechanismforphosphodiesterbondcleavageperformedbynanozymes AT riccardilaura onthemetalaidedcatalyticmechanismforphosphodiesterbondcleavageperformedbynanozymes AT francoulloasebastian onthemetalaidedcatalyticmechanismforphosphodiesterbondcleavageperformedbynanozymes AT milanemil onthemetalaidedcatalyticmechanismforphosphodiesterbondcleavageperformedbynanozymes AT scriminpaolo onthemetalaidedcatalyticmechanismforphosphodiesterbondcleavageperformedbynanozymes AT mancinfabrizio onthemetalaidedcatalyticmechanismforphosphodiesterbondcleavageperformedbynanozymes AT devivomarco onthemetalaidedcatalyticmechanismforphosphodiesterbondcleavageperformedbynanozymes |