Enzyme-Driven, Switchable Catalysis Based on Dynamic Self-Assembly of Peptides

Qing Li, Jiwei Min, Jiaxing Zhang, Meital Reches, Yuhe Shen, Rongxin Su, Yuefei Wang, Wei Qi

Research output: Contribution to journalArticlepeer-review

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 languageAmerican English
Article numbere202309830
JournalAngewandte Chemie - International Edition
Volume62
Issue number41
DOIs
StatePublished - 9 Oct 2023

Keywords

  • Dynamic Self-Assembly
  • Enzyme Mimics
  • Enzyme-Driven
  • Phosphorylation Switch
  • Switchable Catalysis

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • Catalysis

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