Self-assembly of fibril-forming histidine-rich peptides for cofactor-free oxidase-mimetic catalysis

Most oxidases rely on the cofactors for catalyzing the electron transfer reactions, while tend to suffer from externally-induced protein unfolding, cofactor dissociation and nonrecovery of the activities. We have previously demonstrated that the self-assembled oligohistidine peptides, without assistance of the heme cofactor, can mimic the catalytic function of the heme-dependent peroxidases that promoted H2O2 reduction reactions. Herein, we conjugate a fibril-forming peptide to the oligohistidine, to guide the self-assembly of the heme-free catalyst into amyloid-like structures, which facilitate the association of the histidine residues. The modified oligohistidine materials are able to catalyze H2O2 reduction reactions efficiently through the formation of reactive ternary complex intermediates, similar to the mechanism to the unmodified oligohistdine, but the catalytic efficiency is over one order of magnitude higher. Moreover, the catalyst can be switched between inactive and active state without loss of activity for more than ten cycles of heating/cooling treatments, and showed selective oxidation of benzidine substrates over phenolic substrates. These results may aid the future design of the robust cofactor-free supramolecular catalysts and support the evolutionary link between the primitive amyloids and modern-day enzymes.