Structural and functional (catalytic) analyses of several modified PFK sequences shed light on the structural determinants and distinct residues contributing to PFK amyloid catalytic activities (Figure ). The PFK-derived variant analysis confirms that fibril formation is critical for the catalytic activity of PFK. Indeed, the alternating hydrophobic-hydrophilic pattern of PFK has key functional roles: the amphiphilic pattern induces cross-strand fibril architecture, burying the hydrophobic residues while exposing the cationic sidechains. The fibrillar organization further docking of the β-lactam substrates through electrostatic affinity to the lysine sidechains. Indeed, PFK itself was not catalytic in conditions that were not conducive to fibril formation -either low peptide concentrations, or decreased ionic strength (Figure ); both scenarios promote soluble polyproline type-II structure rather than fibril formation .