title: Effects of hesperidin, a flavanone glycoside interaction on the conformation, stability, and aggregation of lysozyme: multispectroscopic and molecular dynamic simulation studies?
abstract: Hesperidin (HESP), a flavanone glycoside, shows high antioxidant properties and possess ability to go through the blood-brain barrier. Therefore, it could be a potential drug molecule against aggregation based diseases such as Alzheimer's, Parkinson's, and systemic amyloidoses. In this work, we investigated the potential of HESP to interact with hen egg-white lysozyme (HEWL) monomer and prevent its aggregation. The HESP-HEWL binding studies were performed using a fluorescence quenching technique, molecular docking and molecular dynamics simulations. We found a strong interaction of HESP with the lysozyme monomer (Ka, ~ 5 × 10(4) M(-1)) mainly through hydrogen bonding, water bridges, and hydrophobic interactions. We showed that HESP molecule spanned the highly aggregation prone region (amino acid residues 48-101) of HEWL and prevented its fibrillar aggregation. Further, we found that HESP binding completely inhibited amorphous aggregation of the protein induced by disulfide-reducing agent tries-(2-carboxyethyl) phosphine. Conformational and stability studies as followed by various tertiary and secondary structure probes revealed that HESP binding only marginally affected the lysozyme monomer conformation and increased both stability and reversibility of the protein against thermal denaturation. Future studies should investigate detail effects of HESP on solvent dynamics, structure, and toxicity of various aggregates. The answers to these questions will not only target the basic sciences, but also have application in biomedical and biotechnological sciences.
authors.affiliation: a UM-DAE Centre for Excellence in Basic Sciences , University of Mumbai , Vidhyanagari Campus, Mumbai 400098 , India.
authors.forename: Aditi
authors.initials: A
authors.lastname: Ratnaparkhi
authors.forename: Shivani A
authors.initials: SA
authors.lastname: Muthu
authors.forename: Sonali M
authors.initials: SM
authors.lastname: Shiriskar
authors.forename: Raghuvir R S
authors.initials: RR
authors.lastname: Pissurlenkar
authors.forename: Sinjan
authors.initials: S
authors.lastname: Choudhary
authors.forename: Basir
authors.initials: B
authors.lastname: Ahmad
mesh_terms: D000818:Animals; D002645:Chickens; D004795:Enzyme Stability / Q000187:drug effects*; D006569:Hesperidin / Q000737:chemistry* / Q000494:pharmacology; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009113:Muramidase / Q000737:chemistry* / Q000378:metabolism; D066329:Protein Aggregates / Q000187:drug effects; D011487:Protein Conformation / Q000187:drug effects*; D014867:Water / Q000737:chemistry
chemical_list: D066329:Protein Aggregates; D014867:Water; D006569:Hesperidin; C421864:hen egg lysozyme; D009113:Muramidase
keywords: aggregation inhibition; fluorescence quenching; ligand–protein binding; molecular dynamics simulations; optical spectroscopy; protein misfolding