An In Vitro elucidation of the antiaggregatory potential of Diosminover thermally induced unfolding of hen egg white lysozyme; A preventive quest for lysozyme amyloidosis

Mohammad Furkan, Mohammad Khursheed Siddiqi, Syed Mohammad Zakariya, Faez Iqbal Khan, Md Imtaiyaz Hassan, Rizwan Hasan Khan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

Protein misfolding diseases are associated with human pathologies. These neurodegenerative diseases remain challenging task for researchers because of their adverse effect on vital organs system. Lysozyme amyloidosis is also associated with multi-organ dysfunction. Hence elucidation of its folding pathway is of great importance, for which hen egg white lysozyme (HEWL) being homological to its human counterpart was taken into consideration. Here in this study we have investigated the effect of diosmin (DSN), a flavonoid over thermally aggregated HEWL. Decrease in ANS, ThT and Rayleigh scattering fluorescence intensity suggests the transition between β to α conformations. Further decrease in absorbance at 360 nm and of congo red with slight blue shift also indicated the disappearance of β sheeted structure under the under the influence of increasing concentration of DSN. These results were also supported by circular dichroism in which gradual appearance α helical structure was observed. Finally visualization under transmission electron microscopy (TEM) authenticated the maximum structural alteration in the previously formed aggregates of HEWL at 250 μM DSN. Molecular docking followed by 100 ns MD simulations help to understand the interaction mechanism of HEWL with DSN. Results suggest DSN could be a useful in the treatment of amyloid related disorders.

Original languageEnglish
Pages (from-to)1015-1023
Number of pages9
JournalInternational Journal of Biological Macromolecules
Volume129
DOIs
Publication statusPublished - 15 May 2019
Externally publishedYes

Keywords

  • Aggregation
  • Diosmin
  • Hen egg white lysozyme (HEWL)
  • MD simulation
  • TEM

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