Short peptide-based cross-β amyloids exploit dual residues for phosphoesterase like activity

Abstract

Herein, we report that short peptides are capable of exploiting their anti-parallel registry to access cross-β stacks to expose more than one catalytic residue, exhibiting the traits of advanced binding pockets of enzymes. Binding pockets decorated with more than one catalytic residue facilitate substrate binding and process kinetically unfavourable chemical transformations. The solvent-exposed guanidinium and imidazole moieties on the cross-β microphases synergistically bind to polarise and hydrolyse diverse kinetically stable model substrates of nucleases and phosphatase. Mutation of either histidine or arginine results in a drastic decline in the rate of hydrolysis. These results not only support the argument of short amyloid peptides as the earliest protein folds but also suggest their interactions with nucleic acid congeners, foreshadowing the mutualistic biopolymer relationships that fueled the chemical emergence of life.

Graphical abstract: Short peptide-based cross-β amyloids exploit dual residues for phosphoesterase like activity

Supplementary files

Article information

Article type
Edge Article
Submitted
08 Jun 2022
Accepted
17 Jul 2022
First published
18 Jul 2022
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2022, Advance Article

Short peptide-based cross-β amyloids exploit dual residues for phosphoesterase like activity

C. Mahato, S. Menon, A. Singh, S. P. Afrose, J. Mondal and D. Das, Chem. Sci., 2022, Advance Article , DOI: 10.1039/D2SC03205H

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