Insights into the mechanism of how Morin suppresses amyloid fibrillation of hen egg white lysozyme

Chong, Xiaoying; Sun, Lijuan; Sun, Yonghui; Chang, Lin; Chang, Alan K.; Lu, Xiaoping; Zhou, Xuejie; Liu, Junqing; Zhang, Bing; Jones, Gary W.; He, Jing

doi:10.1016/j.ijbiomac.2017.03.107

Cited by 10 publications

(3 citation statements)

References 25 publications

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“…There are many reports demonstrating that polyphenols are effective inhibitors of protein fibrillation [ 12 , 13 , 17 – 20 ], through interaction with one or more of the amyloidogenic species, produced during the course of the aggregation process. For instance, some polyphenols prevent amyloid formation by interacting with and stabilizing native structure of proteins [ 47 , 58 , 61 ]; while others bind to prefibrillar structures and redirect amyloidogenic polypeptides into unstructured, off-pathways oligomers [ 62 ], or toward an alternative non-toxic disordered (amorphous) aggregation pathway [ 20 ]. Recently, Hirohata et al .…”

Section: Resultsmentioning

confidence: 99%

Inhibition of HEWL fibril formation by taxifolin: Mechanism of action

et al. 2017

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Among therapeutic approaches for amyloid-related diseases, attention has recently turned to the use of natural products as effective anti-aggregation compounds. Although a wealth of in vitro and in vivo evidence indicates some common inhibitory activity of these compounds, they don’t generally suggest the same mechanism of action. Here, we show that taxifolin, a ubiquitous bioactive constituent of foods and herbs, inhibits formation of HEWL amyloid fibrils and their related toxicity by causing formation of very large globular, chain-like aggregates. A range of amyloid-specific techniques were employed to characterize this process. We found that taxifolin exerts its effect by binding to HEWL prefibrillar species, rather than by stabilizing the molecule in its native-like state. Furthermore, it’s binding results in diverting the amyloid pathway toward formation of very large globular, chain-like aggregates with low β-sheet content and reduced solvent-exposed hydrophobic patches. ThT fluorescence measurements show that the binding capacity of taxifolin is significantly reduced, upon generation of large protofibrillar aggregates at the end of growth phase. We believe these results may help design promising inhibitors of protein aggregation for amyloid-related diseases.

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Section: Resultsmentioning

confidence: 99%

Inhibition of HEWL fibril formation by taxifolin: Mechanism of action

et al. 2017

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“…At a low concentration, bound SA interacts directly with BSA in a site-specific manner: the native structure of protein is stabilized, resulting in a reduced exposure of the partially unfolded protein surface upon heating. At higher concentrations, non-bound (free) SA present in excess may interact with the protein surface, with displacement of the solvent molecules and thereby screening the solvent-protein interaction and enhancing the thermal stability of the later [55]. Presented CD data revealed both conformational changes induced by SA binding that stabilizes the protein structure, and the protein partial unfolding after incubation at higher temperature.…”

Section: Discussionmentioning

confidence: 92%

Impact of Sinapic Acid on Bovine Serum Albumin Thermal Stability

Precupas,

Popa

2024

IJMS

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The thermal stability of bovine serum albumin (BSA) in Tris buffer, as well as the effect of sinapic acid (SA) on protein conformation were investigated via calorimetric (differential scanning microcalorimetry—μDSC), spectroscopic (dynamic light scattering—DLS; circular dichroism—CD), and molecular docking approaches. μDSC data revealed both the denaturation (endotherm) and aggregation (exotherm) of the protein, demonstrating the dual effect of SA on protein thermal stability. With an increase in ligand concentration, (i) protein denaturation shifts to a higher temperature (indicating native form stabilization), while (ii) the aggregation process shifts to a lower temperature (indicating enhanced reactivity of the denatured form). The stabilization effect of SA on the native structure of the protein was supported by CD results. High temperature (338 K) incubation induced protein unfolding and aggregation, and increasing the concentration of SA altered the size distribution of the protein population, as DLS measurements demonstrated. Complementary information offered by molecular docking allowed for the assessment of the ligand binding within the Sudlow’s site I of the protein. The deeper insight into the SA–BSA interaction offered by the present study may serve in the clarification of ligand pharmacokinetics and pharmacodynamics, thus opening paths for future research and therapeutic applications.

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“…ANS can bind to the fibrillar species of HEWL resulting in marked enhancement of the intensity of fluorescence along with a blue shift of the emission maximum from around 510 to 480 nm. 89,90 Before the commencement of amyloid fibrillation conformational changes take place in HEWL which lead to the exposure of hydrophobic regions in HEWL. Thus, monitoring the degree of hydrophobic exposure can serve as a useful tool for studying the fibrillation process.…”

Section: Ans Assaymentioning

confidence: 99%