Dataset Information

Conformational Ensemble of hIAPP Dimer: Insight into the Molecular Mechanism by which a Green Tea Extract inhibits hIAPP Aggregation.

ABSTRACT: Small oligomers formed early along human islet amyloid polypeptide (hIAPP) aggregation is responsible for the cell death in Type II diabetes. The epigallocatechin gallate (EGCG), a green tea extract, was found to inhibit hIAPP fibrillation. However, the inhibition mechanism and the conformational distribution of the smallest hIAPP oligomer - dimer are mostly unknown. Herein, we performed extensive replica exchange molecular dynamic simulations on hIAPP dimer with and without EGCG molecules. Extended hIAPP dimer conformations, with a collision cross section value similar to that observed by ion mobility-mass spectrometry, were observed in our simulations. Notably, these dimers adopt a three-stranded antiparallel ?-sheet and contain the previously reported ?-hairpin amyloidogenic precursor. We find that EGCG binding strongly blocks both the inter-peptide hydrophobic and aromatic-stacking interactions responsible for inter-peptide ?-sheet formation and intra-peptide interaction crucial for ?-hairpin formation, thus abolishes the three-stranded ?-sheet structures and leads to the formation of coil-rich conformations. Hydrophobic, aromatic-stacking, cation-? and hydrogen-bonding interactions jointly contribute to the EGCG-induced conformational shift. This study provides, on atomic level, the conformational ensemble of hIAPP dimer and the molecular mechanism by which EGCG inhibits hIAPP aggregation.

SUBMITTER: Mo Y

PROVIDER: S-EPMC5020610 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Conformational Ensemble of hIAPP Dimer: Insight into the Molecular Mechanism by which a Green Tea Extract inhibits hIAPP Aggregation.

Mo Yuxiang Y Lei Jiangtao J Sun Yunxiang Y Zhang Qingwen Q Wei Guanghong G

Scientific reports 20160913

Small oligomers formed early along human islet amyloid polypeptide (hIAPP) aggregation is responsible for the cell death in Type II diabetes. The epigallocatechin gallate (EGCG), a green tea extract, was found to inhibit hIAPP fibrillation. However, the inhibition mechanism and the conformational distribution of the smallest hIAPP oligomer - dimer are mostly unknown. Herein, we performed extensive replica exchange molecular dynamic simulations on hIAPP dimer with and without EGCG molecules. Exte ...[more]

PMID: 27620620

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Project description:Colorectal cancer is the third most common form of cancer found in the United States. To date surgical resection provides the best chance for cure. Unfortunately, despite "curative" surgery, tumor recurrences develop in 30-40% of patients from either unforeseen residual metastases or from viable tumor cells shed into the circulation before or at the time of surgery. There is evidence from both humans and mice suggesting that tumor growth is stimulated after surgery for a period of time. This study calls for the administration of a green tea extract and a milk thistle extract, two orally ingested supplements, during the week immediately before and weeks after your surgery. It is not the current standard of care to give anti-cancer drugs during the perioperative period. The basic idea behind this study is that it should be beneficial to inhibit cancer growth in the days leading up to and following surgery. Why is this the case? It makes sense to limit or inhibit tumor growth before surgery with drugs provided it can be done safely and does not interfere with the surgery. It is also logical to give anti-cancer drugs after surgery because, unfortunately, about 35 percent of colorectal cancer patients, after resection, have hidden tumor cells that remain in the body. There is also strong human evidence that tumor growth is stimulated during the first month after tumor resection as a result of the surgical injuries and the healing process. Therefore, there is good reason to give anti-cancer drugs as soon as possible after surgery in order to offset some of surgery’s negative effects. Although both supplements have been given safely to a wide variety of patients with a number of different medical problems, the two supplements together have never been given to cancer patients during the weeks just before and following surgery. The researchers hypothesize that the administration of these two supplements together will be safe in the period surrounding colorectal cancer surgery.

Dataset Information

Conformational Ensemble of hIAPP Dimer: Insight into the Molecular Mechanism by which a Green Tea Extract inhibits hIAPP Aggregation.

Publications

Conformational Ensemble of hIAPP Dimer: Insight into the Molecular Mechanism by which a Green Tea Extract inhibits hIAPP Aggregation.

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