Inhibition of copper-induced aggregation of human γD-crystallin by rutin and studies on its role in molecular level for enhancing the chaperone activity of human αA-crystallin by using multi-spectroscopic techniques.

Authors:
Priyanka Chauhan
Priyanka Chauhan
University of Delhi South Campus
India

Spectrochim Acta A Mol Biomol Spectrosc 2019 Jul 10;218:229-236. Epub 2019 Apr 10.

Department of Chemistry, National Institute of Technology Hamirpur, Himachal Pradesh 177005, India. Electronic address:

Oxidative aggregation of γ-crystallins induced by copper in aged lens increases the lens opacity and causes cataract formation. Therefore, chelation of free Cu by small molecules can inhibit metal-mediated aggregation of γ-crystallin. In this work, the inhibition potency of several naturally occurring flavonoid compounds was studied against aggregation of human γD-crystallin (HGD) mediated by copper ions. Among them, rutin demonstrated ~20% inhibition of HGD aggregation induced by Cu through its metal chelation ability. Not only that, the chaperone activity of lens chaperone, human αA-crystallin (HAA) was found to be enhanced in the presence of rutin. Subsequently, the molecular interactions between HAA and rutin were investigated using fluorescence and CD spectroscopy to understand the molecular basis of the chaperone activity enhancement by rutin. Quenching of HAA fluorescence by rutin with a quenching constant in the order of ~10 M depicts a complexation between them. Entropy driven process of complexation between HAA and rutin suggests significant involvement of hydrophobic interactions. Fluorescence resonance energy transfer between protein and ligand can occur at a distance of 2.73 nm. Synchronous fluorescence and circular dichroism spectroscopy revealed that protein-ligand interaction does not cause any notable conformational changes in HAA. Experimental observations have been well substantiated by docking.

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http://dx.doi.org/10.1016/j.saa.2019.04.013DOI Listing
July 2019
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