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The aim of this study is to purify and introduce natural ACE inhibitors extracted from <jats:italic>Zizyphus jujuba<\/jats:italic> fruits. Proteins from <jats:italic>Zizyphus jujuba<\/jats:italic> were lysed by trypsin, papain and their combination. Acquired peptides were purified and evaluated for ACE inhibitory activity. Peptide fractions with inhibitory activity were sequenced using tandem mass spectrometry. To elucidate the mode of peptide binding to ACE, homology modeling, molecular docking and molecular dynamics simulation were performed. Amino acid sequence of F2 and F4 peptides, which were the most active hydrolysates, were determined to be IER and IGK with the IC<jats:sub>50<\/jats:sub> values of 0.060 and 0.072\u2009mg\/ml, respectively. Results obtained by computational analysis revealed that similar to the common ACE competitive inhibitors such as captopril, IER tripeptide binds to the enzyme active site, in vicinity of the zinc binding site, and occupies the S1 and S2\u2019 subsites. Binding occurs through hydrogen bonding with Gln293, Lys522, His524, Tyr531 and also several hydrophobic interactions. Collectively, these findings indicate that IER tripeptide inhibits the rabbit ACE enzyme through a competitive mechanism of inhibition with IC<jats:sub>50<\/jats:sub> values in the millimolar range.<\/jats:p>","DOI":"10.1038\/s41598-020-60972-w","type":"journal-article","created":{"date-parts":[[2020,3,4]],"date-time":"2020-03-04T11:02:30Z","timestamp":1583319750000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Purification, Characterization and Mechanistic Evaluation of Angiotensin Converting Enzyme Inhibitory Peptides Derived from Zizyphus Jujuba Fruit"],"prefix":"10.1038","volume":"10","author":[{"given":"Mina","family":"Memarpoor-Yazdi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadi","family":"Zare-Zardini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navid","family":"Mogharrab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila","family":"Navapour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,4]]},"reference":[{"key":"60972_CR1","first-page":"429","volume":"5","author":"A Salvetti","year":"1985","unstructured":"Salvetti, A. et al. 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