engleski

Esterase sequence composition patterns as inspiration for the design of short catalytic peptides

Ester hydrolysis is of wide biomedical interest, ranging from the environmentally friendly synthesis of pharmaceuticals to the development of biomaterials. Existing peptide-based catalysts exhibit low catalytic efficiency compared to natural enzymes, which is due to the conformational heterogeneity of peptides. Moreover, the correlation between the primary sequence and the catalytic function is not yet well understood. First, we statistically analyzed 22 enzymes that use unique triad mechanisms to perform ester hydrolysis (EC 3.1). We extended this analysis to 974 homologues to verify the identified microenvironment motifs. The goal was to identify sequence-level patterns that will better inform the creation of short peptides that contain important information for catalysis based on the catalytic triad, oxyanion holes, and microenvironments of triad residues. The results showed highly conserved catalytic sites with distinct positional patterns, chemical microenvironments conducive to catalysis, and revealed variations in the composition of catalytic sites that could be useful for the design of minimalistic catalysts. Linear and cyclic peptides were then synthesized and their ability to catalyze pNPA hydrolysis was tested. Control over the catalytic performance of peptides was achieved through modifications at the sequence level and by varying the chemical environment.

Microenvironments ; alignment ; enzymes ; catalytic ; hydrolysis

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