Biological evaluation and interaction mechanism of beta-site APP cleaving enzyme 1 inhibitory pentapeptide from egg albumin
Inhibition of beta-site APP cleaving enzyme1 (BACE1) is one of the most promising therapeutic approaches for Alzheimer’s disease. To find natural products for the treatment of Alzheimer's disease, absorption, distribution, metabolism, excretion and toxicity (ADMET) properties and in vitro BACE1...
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| Format: | Article |
| Language: | English |
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Tsinghua University Press
2020-06-01
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| Series: | Food Science and Human Wellness |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213453019301740 |
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| author | Zhipeng Yu Sijia Wu Wenzhu Zhao Long Ding David Shiuan Fuping Zheng Jianrong Li Jingbo Liu |
| author_facet | Zhipeng Yu Sijia Wu Wenzhu Zhao Long Ding David Shiuan Fuping Zheng Jianrong Li Jingbo Liu |
| author_sort | Zhipeng Yu |
| collection | DOAJ |
| description | Inhibition of beta-site APP cleaving enzyme1 (BACE1) is one of the most promising therapeutic approaches for Alzheimer’s disease. To find natural products for the treatment of Alzheimer's disease, absorption, distribution, metabolism, excretion and toxicity (ADMET) properties and in vitro BACE1 inhibitory activity of the peptides isolated from egg albumin were evaluated. Then, molecular docking and molecular dynamics simulation were used to explain the molecular mechanism of the interactions between BACE1 and peptides. The IC50 value of peptide KLPGF, with satisfactory ADMET properties, against BACE1 was (8.30 ± 0.56) mmol/L. Molecular docking revealed that KLPGF contacted with the residues of BACE1’s active sites through twelve hydrogen bonds interactions, two hydrophobic interactions, one electrostatic interaction, and two Pi-cation interactions. The 5 ns molecular dynamics simulations confirmed that the structure of KLPGF with BACE1 was stable. Peptide KLPGF contacted the residues Lys321, Asp228, and Asn233 with stable hydrogen bonds. KLPGF may be a potential anti-BACE1 candidate. |
| format | Article |
| id | doaj-art-d044209f42e04a13874890f809945b59 |
| institution | Kabale University |
| issn | 2213-4530 |
| language | English |
| publishDate | 2020-06-01 |
| publisher | Tsinghua University Press |
| record_format | Article |
| series | Food Science and Human Wellness |
| spelling | doaj-art-d044209f42e04a13874890f809945b592025-02-03T05:38:41ZengTsinghua University PressFood Science and Human Wellness2213-45302020-06-0192162167Biological evaluation and interaction mechanism of beta-site APP cleaving enzyme 1 inhibitory pentapeptide from egg albuminZhipeng Yu0Sijia Wu1Wenzhu Zhao2Long Ding3David Shiuan4Fuping Zheng5Jianrong Li6Jingbo Liu7College of Food Science and Engineering, National & Local Joint Engineering Research Center of Storage, Processing and Safety Control Technology for Fresh Agricultural and Aquatic Products, Bohai University, Jinzhou, 121013, PR China; Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University (BTBU), Beijing, 102488, PR ChinaCollege of Food Science and Engineering, National & Local Joint Engineering Research Center of Storage, Processing and Safety Control Technology for Fresh Agricultural and Aquatic Products, Bohai University, Jinzhou, 121013, PR ChinaCollege of Food Science and Engineering, National & Local Joint Engineering Research Center of Storage, Processing and Safety Control Technology for Fresh Agricultural and Aquatic Products, Bohai University, Jinzhou, 121013, PR China; Corresponding author at: Jinzhou City, Liaoning Province, PR China.College of Food Science and Engineering, Northwest A&F University, Yangling, 712100, PR ChinaCollege of Food Science and Engineering, National & Local Joint Engineering Research Center of Storage, Processing and Safety Control Technology for Fresh Agricultural and Aquatic Products, Bohai University, Jinzhou, 121013, PR ChinaBeijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University (BTBU), Beijing, 102488, PR China; Corresponding authors.College of Food Science and Engineering, National & Local Joint Engineering Research Center of Storage, Processing and Safety Control Technology for Fresh Agricultural and Aquatic Products, Bohai University, Jinzhou, 121013, PR China; Corresponding authors.Lab of Nutrition and Functional Food, Jilin University, Changchun, 130062, PR China; Corresponding authors.Inhibition of beta-site APP cleaving enzyme1 (BACE1) is one of the most promising therapeutic approaches for Alzheimer’s disease. To find natural products for the treatment of Alzheimer's disease, absorption, distribution, metabolism, excretion and toxicity (ADMET) properties and in vitro BACE1 inhibitory activity of the peptides isolated from egg albumin were evaluated. Then, molecular docking and molecular dynamics simulation were used to explain the molecular mechanism of the interactions between BACE1 and peptides. The IC50 value of peptide KLPGF, with satisfactory ADMET properties, against BACE1 was (8.30 ± 0.56) mmol/L. Molecular docking revealed that KLPGF contacted with the residues of BACE1’s active sites through twelve hydrogen bonds interactions, two hydrophobic interactions, one electrostatic interaction, and two Pi-cation interactions. The 5 ns molecular dynamics simulations confirmed that the structure of KLPGF with BACE1 was stable. Peptide KLPGF contacted the residues Lys321, Asp228, and Asn233 with stable hydrogen bonds. KLPGF may be a potential anti-BACE1 candidate.http://www.sciencedirect.com/science/article/pii/S2213453019301740Alzheimer’s diseaseBACE1ADMET predictionMolecular dockingMolecular dynamicsKLPGF |
| spellingShingle | Zhipeng Yu Sijia Wu Wenzhu Zhao Long Ding David Shiuan Fuping Zheng Jianrong Li Jingbo Liu Biological evaluation and interaction mechanism of beta-site APP cleaving enzyme 1 inhibitory pentapeptide from egg albumin Food Science and Human Wellness Alzheimer’s disease BACE1 ADMET prediction Molecular docking Molecular dynamics KLPGF |
| title | Biological evaluation and interaction mechanism of beta-site APP cleaving enzyme 1 inhibitory pentapeptide from egg albumin |
| title_full | Biological evaluation and interaction mechanism of beta-site APP cleaving enzyme 1 inhibitory pentapeptide from egg albumin |
| title_fullStr | Biological evaluation and interaction mechanism of beta-site APP cleaving enzyme 1 inhibitory pentapeptide from egg albumin |
| title_full_unstemmed | Biological evaluation and interaction mechanism of beta-site APP cleaving enzyme 1 inhibitory pentapeptide from egg albumin |
| title_short | Biological evaluation and interaction mechanism of beta-site APP cleaving enzyme 1 inhibitory pentapeptide from egg albumin |
| title_sort | biological evaluation and interaction mechanism of beta site app cleaving enzyme 1 inhibitory pentapeptide from egg albumin |
| topic | Alzheimer’s disease BACE1 ADMET prediction Molecular docking Molecular dynamics KLPGF |
| url | http://www.sciencedirect.com/science/article/pii/S2213453019301740 |
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