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(\u2212)\u2010Epigallocatechin gallate (EGCG) can bind amyloid proteins to inhibit the fibrillation of these proteins. However, the mechanic detail of EGCG inhibiting amyloid formation is still unclear at the molecular level. In the present work, we sought to investigate the effect of EGCG on amidated hIAPP (hIAPP\u2010NH<jats:sub>2<\/jats:sub>) fibrillation and aggregation by using spectroscopic and microscopic techniques, and also sought to gain insights into the interaction of EGCG and hIAPP<jats:sub>22\u201327<\/jats:sub> by using spectroscopic experiments and quantum chemical calculations. ThT fluorescence, real\u2010time NMR, and TEM studies demonstrated that EGCG inhibits the formation of hIAPP\u2010NH<jats:sub>2<\/jats:sub> fibrils, while promoting the formation of hIAPP\u2010NH<jats:sub>2<\/jats:sub> amorphous aggregates. Phenylalanine intrinsic fluorescence and NMR studies of the EGCG\/hIAPP<jats:sub>22\u201327<\/jats:sub> complex revealed three important binding sites including the A ring of EGCG, residue Phe23, and residue Ile26. DFT calculations identified the dominant binding structures of EGCG\/Phe23 and EGCG\/Ile26 complexes, named structure\u2005I and structure\u2005II, respectively. Our study demonstrates the inhibitory mechanism of EGCG on fibrillation and aggregation of hIAPP\u2010NH<jats:sub>2<\/jats:sub> in which EGCG interacts with hIAPP\u2010NH<jats:sub>2<\/jats:sub> through hydrogen bonding and \u03c0\u2013\u03c0 interactions between the A ring and residue Phe23 as well as hydrophobic interactions between the A ring and residue Ile26, which can thus inhibit the interpeptide interaction between hIAPP\u2010NH<jats:sub>2<\/jats:sub> monomers and finally inhibit fibrillation of hIAPP\u2010NH<jats:sub>2<\/jats:sub>. This study agrees with and reinforces previous studies and offers an intuitive explanation at both the atomic and molecular levels. Our findings may provide an invaluable reference for the future development of new drugs in the management of diabetes.<\/jats:p>","DOI":"10.1002\/cphc.201700057","type":"journal-article","created":{"date-parts":[[2017,3,15]],"date-time":"2017-03-15T12:42:43Z","timestamp":1489581763000},"page":"1611-1619","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Inhibitory Mechanism of Epigallocatechin Gallate on Fibrillation and Aggregation of Amidated Human Islet Amyloid Polypeptide"],"prefix":"10.1002","volume":"18","author":[{"given":"Zhi\u2010Xue","family":"Xu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Molecular Engineering of Polymers Department of Macromolecular Science Fudan University  Shanghai 200433 P. R. 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