In parallel, the ubiquitous lysine sidechains partake in nucleophilic attacks on the β-lactam rings, resulting in their destabilization and subsequent hydrolysis. The decreased pKa value of the primary amine side chains of the PFK fibrils rather than the peptide monomers (Figure ) further attests to the enhanced reactivity of the amines on the fibril surface. This model echoes reported activities of serine nucleophiles in β-lactamases, in which deprotonated serine residues at the active sites act as nucleophiles, forming covalent acyl-enzyme intermediates via the carbonyl units in the β-lactam ring . Other studies reported that metal ions in metal-β-lactamases activate water molecules, which similarly attack the carbonyl residues in the β-lactam ring . In both enzyme systems, a water molecule hydrolyzes the acyl-enzyme intermediates, consequently releasing the inactivated β-lactam substrate. The presumed similarity between the catalytic properties of PFK amyloid fibrils and β-lactamase enzymes is supported by the observation that an anti-β-lactamase polyclonal antibody successfully inhibited PFK amyloid fibril-induced β-lactam hydrolysis (Figure ). Further structural insight is furnished through application of cryo-EM, revealing a remarkable βlactam-induced PFK coiled-fiber organization. This observation underlies the catalytic mechanism, particularly the allosteric behavior. Specifically, the negatively charged nitrocefin substrate initially binds to the PFK fibrils through electrostatic interactions with the lysine sidechains. In higher nitrocefin concentrations, the abundance of negative charge gives rise to inversion of the fibrils' surface potential (apparent in the nitrocefin-dependent ζ-potential analysis, Figure ) giving rise to complexation of two adjoining PFK amyloid fibrils through the central interweaved nitrocefin array, forming the coiled fibril organization. Importantly, the coiled fibril assembly likely enhances the catalytic activity via nucleophilic attacks of the abundant lysine sidechains on the β-lactam four-member rings of the embedded substrate molecules. Furthermore, the coiled fibrils may accelerate the catalytic activity by creating physical barrier for substrate diffusion, thereby increasing the probability of the substrate to engage with the nucleophilic residues on the PFK fibrils' surface. Notably, recent studies have emphasized the significance of allosteric mechanisms in catalysis induced by short peptide assemblies .