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Enzymatic self-assembly/disassembly turns “ON”/“OFF” the mimetic hydrolytic activity of histidine nanofibers

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Abstract

Mimetic enzymes are devised as alternates or supplements of natural enzymes in broad fields but regulating their activities in a switchable manner remains challenging. Herein, we proposed an enzymatic self-assembly/disassembly strategy to address this issue. A peptide molecule NapFFEYIH (YH) was rationally designed which, after self-assembling into nanofibers, lined up the histidine moieties to form active hydrolysis centers for mimicking hydrolase activity. Enzymatic dephosphorylation of NapF-FEYpIH (YpH) by alkaline phosphatase to yield YH also turned “ON” the hydrolase activity. In turn, phosphorylation of YH by phosphokinase epidermal growth factor receptor to yield YpH disassembled the nanofibers and thus turned the activity “OFF”. As such, the “ON”/“OFF” of the mimetic hydrolase activities could be regulated under physiological conditions through ALP/EGFR-mediated self-assembly/disassembly of histidine nanofibers. This work provides a feasible strategy for the on-demand fabrication of artificial enzymes with controllable and superior activities.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (22234002, 22204019, 82172097) and the Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX22_0245).

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Correspondence to Fuqiang Wang or Gaolin Liang.

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Conflict of interest The authors declare no conflict of interest.

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Supporting information The supporting information is available online at chem.scichina.com and link.springer.com/journal/11426. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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Sun, X., Wang, M., Liu, X. et al. Enzymatic self-assembly/disassembly turns “ON”/“OFF” the mimetic hydrolytic activity of histidine nanofibers. Sci. China Chem. 67, 517–522 (2024). https://doi.org/10.1007/s11426-023-1788-5

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  • DOI: https://doi.org/10.1007/s11426-023-1788-5

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