Inhibition of insulin amyloid fibrillation by Morin hydrate

• Published in: International journal of biological macromolecules Vol. 108; pp. 225 - 239
• Main Authors: Patel, Palak, Parmar, Krupali, Das, Mili
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-03-2018
• Subjects: Aggregation propensity; Computational docking; Insulin amyloid fibrillation; Molecular dynamics; Morin hydrate; ThT; CD; Morin hydrate; ANS; RMSF; Molecular dynamics; PME; RMSD; APRs; PDB; LINCS; Computational docking; AIns; Rg; MD; NCBI; hIAPP; Insulin amyloid fibrillation; TEM; Aggregation propensity
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2017.11.168

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•Morin hydrate significantly inhibits amyloid fibrillation of human insulin in a concentration dependent manner.•It binds to insulin with fairly strong affinity.•This molecule binds to insulin and prevents structural and/or conformational changes that lead to amyloid fibrillation.•Morin hydrate most likely binds to fibrils throughout the surface, thereby stabilizing them and inhibiting the release of oligomeric species.
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 -26.436kJmol−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.