Structure-activity relationships in catalytic amyloids

Short peptide-based assemblies combined with metal ions are simple yet effective platforms for catalysis. This study investigates the catalytic properties of de novo amyloid forming peptides, how their catalytic properties change with a range of hydrolysis substrates and the relationship between catalysis and structural characteristics. We have shown that even slight modifications in peptide sequence have a drastic impact on catalytic efficiency and substrate selectivity. We have also established k_uncat benchmarks for a 4-methylumbelliferyl ester that is increasingly reported as a model substrate in protein design studies. Our studies have yielded catalytic amyloids which display levels of specific activity on par with those reported for the best de novo globular enzymes. This work expands the understanding of catalytic amyloid function and explores design principles for developing minimal peptide scaffolds with tunable esterase-like activity.