Many natural enzymes can interact with proteins to produce functional proteins, but the interaction between nanozymes and proteins is less studied. Researchers are now investigating the roles of nanozymes in biological settings and their interactions beyond small molecule substrates.
The potential of nanozymes for biotechnological and therapeutic applications drives this exploration. Additionally, scientists are working on creating advanced artificial enzymes to address the challenges related to the selectivity, specificity, and efficiency of existing artificial enzymes.
Researchers from the CSIR-Central Leather Research Institute (CLRI), working with the support of INSPIRE Faculty Fellowship and WISE Kiran Fellowship of the Department of Science and Technology (DST), investigated the chemistry at the interface of proteins and nanozymes to push the limits of artificial enzymes. Their work aims to use nanozymes as catalysts for transforming biomaterials for their futuristic use in medicinal and biomedical applications.
They mainly studied the significant role of manganese-based oxidase nanozyme (MnN) in stitching collagen, a vital structural protein in various biological tissues. For this, they used a process called ‘crosslinking’ to produce biomaterials.
Their findings revealed that MnN, in combination with an oxidase nanozyme, can activate collagen and promote the covalent crosslinking of its tyrosine residues using a small amount of tannic acid under mild conditions, while preserving the protein’s triple-helical structure. This method highlights the potential of nanozymes and offers an effective solution to enhance collagen’s resistance to collagenase degradation, achieving 100% resistance. This advancement addresses a significant challenge in ensuring the durability of collagen-based biomaterials.
In a separate study, researchers designed a bis-(μ-oxo) di-copper active site within the pores of a metal-organic framework (MOF-808), aiming to mimic enzyme binding pockets and tackle issues of selectivity, specificity, and efficiency in nanozymes. Their findings show that while this approach effectively regulates substrate dynamics and reactivity, it unintentionally reduces oxidase selectivity when small proteins, like cytochrome c, try to access the active site, as they are larger than the pore opening of MOF-808.
This research highlights the importance of carefully designing artificial enzymes using nanomaterials, emphasizing the need for a delicate balance between desired and undesired reactivity to optimize their use in medical applications.
The research expands the scope of nanozymes to interact with complex biological molecules like collagen beyond their traditional role with small molecules. This opens new possibilities for creating biomaterials with intact structural properties for therapeutic use.
The study aims to provide guidelines for developing selective, specific, and highly active next-generation artificial enzymes. Its novelty lies in establishing a new paradigm for nanozyme-protein interactions and emphasizing substrate selectivity in enzyme design, advancing our understanding of nanozyme chemistry for biotechnological and therapeutic applications.
Journal References:
- Adarsh P. Fatrekar, Rasmi V. Morajkarar and Amit A. Vernekar. Expanding limits of artificial enzymes: unprecedented catalysis by an oxidase nanozyme in activating a structural protein for covalent crosslinking and conferring remarkable proteolytic resistance†. Chemical Science. DOI: 10.1039/d4sc03767g
- Rasmi V. Morajkarar, Adarsh P. Fatrekar and Amit A. Vernekar. Approach of a small protein to the biomimetic bis- (m-oxo) dicopper active-site installed in MOF-808 pores with restricted access perturbs substrate selectivity of oxidase nanozyme†. Chemical Science. DOI: 10.1039/d4sc02136c