Interaction and inhibition of lysozyme amyloid fibrillation by benzophenanthridine alkaloid sanguinarine: Photophysical, molecular docking and imaging studies

Abstract

Protein misfolding lead to pathological amyloid aggregates causing neurodegenerative disorders. Interaction and effect of benzophenanthridine alkaloid, sanguinarine (SNR hereafter), on lysozyme fibrillation was studied in the quest for designing potent antiamyloidogenics. SNR quenched the intrinsic fluorescence of lysozyme and the quenching mechanism was static. There existed one type of binding site for SNR on lysozyme and TRP residues were mainly involved in binding. 3D-fluorescence studies indicated conformational changes in lysozyme upon complexation with SNR. The binding between lysozyme and SNR was also studied by molecular docking to understand the forces involved in the binding. Effect of SNR on lysozyme fibrillation was examined from Thioflavin T assay which revealed that SNR suppressed the fibrillation of lysozyme significantly. Nile red and ANS assay revealed that SNR arrested the fibrillation. FTIR and circular dichroism showed that β-sheet content of the fibrillar species was reduced by SNR implying fibrillogenesis was inhibited as amyloid fibrils have β-sheet rich structures. AFM also revealed that SNR induced a marked decrease in the fibrillar quantity. These results can be utilized for designing potential drugs for amyloidosis.