Issue 28, 2024

Approach of a small protein to the biomimetic bis-(μ-oxo) dicopper active-site installed in MOF-808 pores with restricted access perturbs substrate selectivity of oxidase nanozyme

Abstract

Advances in nanozymes have taken shape over the past few years in several domains. However, persisting challenging limitations of selectivity, specificity, and efficiency necessitate careful attention to aid in the development of next-generation artificial enzymes. Despite nanozymes having significant therapeutic and biotechnological prospects, the multienzyme mimetic activities can compromise their intended applications. Furthermore, the lack of substrate selectivity can hamper crucial biological pathways. While working on addressing the challenges of nanozymes, in this work, we aim to highlight the interplay between the substrates and bis-(μ-oxo) dicopper active site-installed MOF-808 for selectively mimicking oxidase. This oxidase mimetic with a small pore-aperture (1.4 nm), similar to the opening of enzyme binding pockets, projects a tight control over the dynamics and the reactivity of substrates, making it distinct from the general oxidase nanozymes. Interestingly, the design and the well-regulated activity of this nanozyme effectively thwart DNA from approaching the active site, thereby preventing its oxidative damage. Crucially, we also show that despite these merits, the oxidase selectivity is compromised by small proteins such as cytochrome c (Cyt c), having dimensions larger than the pore aperture of MOF-808. This reaction lucidly produces water molecules as a result of four electron transfer to an oxygen molecule. Such unintended side reactivities warrant special attention as they can perturb redox processes and several cellular energy pathways. Through this study, we provide a close look at designing next-generation artificial enzymes that can address the complex challenges for their utility in advanced applications.

Graphical abstract: Approach of a small protein to the biomimetic bis-(μ-oxo) dicopper active-site installed in MOF-808 pores with restricted access perturbs substrate selectivity of oxidase nanozyme

Supplementary files

Transparent peer review

To support increased transparency, we offer authors the option to publish the peer review history alongside their article.

View this article’s peer review history

Article information

Article type
Edge Article
Submitted
01 apr. 2024
Accepted
05 jún. 2024
First published
10 jún. 2024
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2024,15, 10810-10822

Approach of a small protein to the biomimetic bis-(μ-oxo) dicopper active-site installed in MOF-808 pores with restricted access perturbs substrate selectivity of oxidase nanozyme

R. V. Morajkar, A. P. Fatrekar and A. A. Vernekar, Chem. Sci., 2024, 15, 10810 DOI: 10.1039/D4SC02136C

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements