Ankaflavin and\nMonascin Prevent Fibrillogenesis of\nHen Egg White Lysozyme: Focus on Noncovalent and Covalent Interactions

Misfolding and amyloid fibrillogenesis of proteins have\nclose relationships\nwith several neurodegenerative diseases. The present work investigates\nthe inhibitive activities of ankaflavin (AK) and monascin (MS), two\nyellow pigments separated from <i>Monascus</i>-fermented\nrice, on hen egg white lysozyme (HEWL) fibrillation. The results demonstrated\nthat AK/MS suppressed HEWL fibrillation through interfering with the\nnucleation period and AK was more potent. Fluorescence quenching and <i>in silico</i> docking studies revealed that AK/MS bond to HEWL\nby the formation of noncovalent forces with some critical amino acid\nresidues that tend to form fibrils. Compared to those of AK, hydrogen\nbonding interactions between MS and Asn46, Trp62, and Trp63 residues\nin HEWL were slightly weaker. Besides, the covalent interaction between\nMS and HEWL with the binding site of Arg68 was found. These observations\noffered reasonable explanations for the difference in the mechanisms\nof AK and MS inhibiting HEWL fibrillogenesis. In a word, all data\nacquired herein indicated AK/MS as potent candidates for the improvement\nand treatment of neurological disorders.