Abstract
Covalent regulatory systems of enzymes are widely used to modulate biological enzyme activities. Inspired by the regulation of reactive-site phosphorylation in organisms, we developed peptide-based catecholase mimetics with switchable catalytic activity and high selectivity through the co-assembly of nanofibers comprising peptides and copper ions (Cu2+). Through careful design and modification of the peptide backbone structure based on the change in the free energy of the system, we identified the peptide with the most effective reversible catalytic activity. Kinase/phosphatase switches were used to control the reversible transition of nanofiber formation and depolymerization, as well as to modulate the active-site microenvironment. Notably, the self-assembly and disassembly processes of nanofibers were simulated using coarse-grained molecular dynamics. Furthermore, theoretical calculations confirmed the coordination of the peptide and Cu2+, forming a zipper-like four-ligand structure at the catalytically active center of the nanofibers. Additionally, we conducted a comprehensive analysis of the catalytic mechanism. This study opens novel avenues for designing biomimetic enzymes with ordered structures and dynamic catalytic activities.
Original language | American English |
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Article number | e202309830 |
Journal | Angewandte Chemie - International Edition |
Volume | 62 |
Issue number | 41 |
DOIs | |
State | Published - 9 Oct 2023 |
Bibliographical note
Funding Information:This work was supported by the Natural Science Foundation of China (Nos. 22278306, 22278314, 22078239), the Seed Foundation of Tianjin University (No. 2023XJD-0067), and the State Key Laboratory of Chemical Engineering (Nos. SKL-ChE-21T03 and SKL-ChE-22T05). The authors thank the staff of Beijing Synchrotron Radiation Facility (BSRF, Beijing, China) for assistance with the SAXS and WAXS experiments.
Funding Information:
This work was supported by the Natural Science Foundation of China (Nos. 22278306, 22278314, 22078239), the Seed Foundation of Tianjin University (No. 2023XJD‐0067), and the State Key Laboratory of Chemical Engineering (Nos. SKL‐ChE‐21T03 and SKL‐ChE‐22T05). The authors thank the staff of Beijing Synchrotron Radiation Facility (BSRF, Beijing, China) for assistance with the SAXS and WAXS experiments.
Publisher Copyright:
© 2023 Wiley-VCH GmbH.
Keywords
- Dynamic Self-Assembly
- Enzyme Mimics
- Enzyme-Driven
- Phosphorylation Switch
- Switchable Catalysis