engleski

Esterase Sequence Composition Patters As Inspiration For The Design Of Short Catalytic Peptides

Ester hydrolysis is of wide biomedical interest, spanning from the green synthesis of pharmaceuticals to biomaterials' development. Existing peptide-based catalysts exhibit low catalytic efficiency compared to natural enzymes, due to the conformational heterogeneity of peptides. Moreover, there is lack of understanding of the correlation between the primary sequence and catalytic function. First, we statistically analyzed 22 EC 3.1 hydrolases with known catalytic triads, characterized by unique mechanisms. We extended this analysis to 974 homologues to verify the identified microenvironment motifs. The aim was to identify patterns at the sequence level that will better inform the creation of short peptides containing important information for catalysis, based on the catalytic triad, oxyanion holes and the triad residues microenvironments. The results showed highly conserved catalytic sites with distinct positional patterns, chemical microenvironments that favor catalysis and revealed variations in catalytic site composition that could be useful for the design of minimalistic catalysts. Next, linear and cyclic peptides were synthesized and their ability to catalyze pNPA hydrolysis was tested. The control over catalytic performance of peptides was achieved through modifications at the sequence level and by varying the chemical environment.

catalytic peptides ; ester hydrolysis ; catalytic triad

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