Journal
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
Volume 33, Issue 9, Pages 1866-1879Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/07391102.2014.975746
Keywords
optical spectroscopy; aggregation inhibition; fluorescence quenching; protein misfolding; ligand-protein binding; molecular dynamics simulations
Categories
Funding
- UM-DAE Centre for Excellence in Basic Sciences
- UGC-Faculty Recharge Programme (UGC-FRP)
- University of Mumbai
Ask authors/readers for more resources
Hesperidin (HESP), a flavanone glycoside, shows high antioxidant properties and posses 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 (K-a, ~ 5x10(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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available