Folding within Frameworks: Confinement in Zr-MOFs Reshapes Enzyme Structure and Catalytic Activity.
- 1Department of Chemistry, KU Leuven, Celestijnenlaan 200F, Leuven3001, Belgium.
- 2Van't Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, Amsterdam1098 XH, The Netherlands.
Abstract
Enhancing the robustness of functional proteins remains a central challenge in biotechnology, with implications for catalysis, pharmaceuticals, and industrial synthesis. Enzyme immobilization in porous materials such as metal-organic frameworks (MOFs) is widely used to enhance enzyme stability; however, the structural state of proteins within these environments is poorly understood and is often assumed to remain largely unchanged. Since enzyme functionality is closely linked to its 3D conformation, the lack of detailed structural information makes the design of enzyme@porous systems largely empirical. In this work, we demonstrate that in situ attenuated total reflectance infrared spectroscopy is a powerful tool for monitoring protein adsorption and confinement in the Zr-based MOF NU-1000. By tracking characteristic amide bands, we monitor changes in protein vibrational signatures that reflect alterations in protein structure and local environment during interaction with the framework. Our results reveal that MOFs are not passive hosts but can induce pronounced perturbations in the protein structure upon adsorption and confinement. We identified a framework-sensitive spectroscopic signature associated with protein uptake into the MOF pore environment and support this assignment through uptake kinetics, diffusion analysis, pore-size controls, and protease accessibility experiments. Protein uptake is governed not only by size compatibility but also by electrostatic interactions, ionic strength, and protein conformational state. Importantly, these immobilization- and confinement-associated structural perturbations correlate with changes in catalytic activity: enhanced catalytic activity for dynamically perturbed proteins and reduced activity for structurally constrained systems. These findings support a relationship between protein-MOF interactions, structural perturbation, and enzymatic function and provide guidelines for tuning protein behavior in MOF-based biocatalysis, separations, and sensing applications.
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BibTeX
@article{swinnen2026folding,
title = {{Folding within Frameworks: Confinement in Zr-MOFs Reshapes Enzyme Structure and Catalytic Activity.}},
author = {Siene Swinnen and Maxim Lox and Marika Di Berto Mancini and Kilian Declerck and Francisco de Azambuja and Tatjana N Parac-Vogt and Bettina Baumgartner},
journal = {Journal of the American Chemical Society},
year = {2026},
month = sep,
doi = {10.1021/jacs.6c11124},
url = {https://europepmc.org/article/MED/42937856},
note = {CC BY},
}
RIS
TY - JOUR
TI - Folding within Frameworks: Confinement in Zr-MOFs Reshapes Enzyme Structure and Catalytic Activity.
AU - Siene Swinnen
AU - Maxim Lox
AU - Marika Di Berto Mancini
AU - Kilian Declerck
AU - Francisco de Azambuja
AU - Tatjana N Parac-Vogt
AU - Bettina Baumgartner
PY - 2026
DA - 2026/09/01
JO - Journal of the American Chemical Society
DO - 10.1021/jacs.6c11124
UR - https://europepmc.org/article/MED/42937856
AB - Enhancing the robustness of functional proteins remains a central challenge in biotechnology, with implications for catalysis, pharmaceuticals, and industrial synthesis. Enzyme immobilization in porous materials such as metal-organic frameworks (MOFs) is widely used to enhance enzyme stability; however, the structural state of proteins within these environments is poorly understood and is often assumed to remain largely unchanged. Since enzyme functionality is closely linked to its 3D conformation, the lack of detailed structural information makes the design of enzyme@porous systems largely empirical. In this work, we demonstrate that in situ attenuated total reflectance infrared spectroscopy is a powerful tool for monitoring protein adsorption and confinement in the Zr-based MOF NU-1000. By tracking characteristic amide bands, we monitor changes in protein vibrational signatures that reflect alterations in protein structure and local environment during interaction with the framework. Our results reveal that MOFs are not passive hosts but can induce pronounced perturbations in the protein structure upon adsorption and confinement. We identified a framework-sensitive spectroscopic signature associated with protein uptake into the MOF pore environment and support this assignment through uptake kinetics, diffusion analysis, pore-size controls, and protease accessibility experiments. Protein uptake is governed not only by size compatibility but also by electrostatic interactions, ionic strength, and protein conformational state. Importantly, these immobilization- and confinement-associated structural perturbations correlate with changes in catalytic activity: enhanced catalytic activity for dynamically perturbed proteins and reduced activity for structurally constrained systems. These findings support a relationship between protein-MOF interactions, structural perturbation, and enzymatic function and provide guidelines for tuning protein behavior in MOF-based biocatalysis, separations, and sensing applications.
SN - 0002-7863
SN - 1520-5126
ER -