Inhibition of insulin amyloid fibrillation by Morin hydrate

Patel, P and Parmar, K and Das, M (2018) Inhibition of insulin amyloid fibrillation by Morin hydrate. In: International Journal of Biological Macromolecules, 108 . pp. 225-239.

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Abstract

We report here the inhibition of amyloid fibrillation of human insulin in vitro by Morin hydrate, a naturally occurring small molecule. Using spectroscopic assays and transmission electron microscopy, we found that Morin hydrate effectively inhibits insulin amyloid fibrillation in a dose dependent manner with more than 80% inhibition occurring even at only a 1:1 concentration. As suggested by fluorescence spectroscopic titration studies, Morin hydrate binds to insulin with a fairly strong affinity of -26.436 kJ mol−1. Circular dichroism (CD) spectroscopy was used to analyse structural changes of insulin in the presence of Morin hydrate demonstrating the ability of Morin hydrate to bind with the native monomeric protein and/or its near native state, intermediate oligomeric species and amyloid fibrils. Based on computational docking and molecular dynamics study, we propose that Morin hydrate binds to residues having greater aggregation propensity and prevent structural and/or conformational changes leading to amyloid fibrillation. Morin hydrate should also bind to fibrils by hydrogen bonding and/or hydrophobic forces throughout the surface, stabilize them and inhibit the release of oligomeric species which could be nuclei or template for further fibrillation. Overall results provide an insight into the mechanism of inhibition of insulin amyloid fibrillation by Morin hydrate.

Item Type:	Journal Article
Publication:	International Journal of Biological Macromolecules
Publisher:	Elsevier B.V.
Additional Information:	The copyright for this article belongs to the Elsevier B.V.
Keywords:	8 anilino 1 naphthalenesulfonic acid; amyloid; insulin; morin; thioflavine; amyloid; amyloid protein; flavonoid; insulin; morin; protein aggregate; protein binding, Article; binding affinity; circular dichroism; conformational transition; drug binding; drug inhibition; drug mechanism; fibril; fluorescence spectroscopy; human; hydrogen bond; in vitro study; molecular docking; molecular dynamics; oligomerization; titrimetry; transmission electron microscopy; chemical phenomena; chemistry; drug effect; metabolism; proteinosis; structure activity relation, Amyloid; Amyloidogenic Proteins; Circular Dichroism; Flavonoids; Humans; Hydrophobic and Hydrophilic Interactions; Insulin; Molecular Docking Simulation; Molecular Dynamics Simulation; Protein Aggregates; Protein Aggregation, Pathological; Protein Binding; Structure-Activity Relationship
Department/Centre:	Autonomous Societies / Centres > Society for Innovation and Development
Date Deposited:	10 Aug 2022 04:58
Last Modified:	10 Aug 2022 04:58
URI:	https://eprints.iisc.ac.in/id/eprint/75645

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