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Identification and confirmation of 14-3-3 ζ as a novel target of ginsenosides in brain tissues
BACKGROUND: Ginseng can help regulate brain excitability, promote learning and memory, and resist cerebral ischemia in the central nervous system. Ginsenosides are the major effective compounds of Ginseng, but their protein targets in the brain have not been determined. METHODS: We screened proteins...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282492/ https://www.ncbi.nlm.nih.gov/pubmed/34295206 http://dx.doi.org/10.1016/j.jgr.2020.12.007 |
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author | Chen, Feiyan Chen, Lin Liang, Weifeng Zhang, Zhengguang Li, Jiao Zheng, Wan Zhu, Zhu Zhu, Jiapeng Zhao, Yunan |
author_facet | Chen, Feiyan Chen, Lin Liang, Weifeng Zhang, Zhengguang Li, Jiao Zheng, Wan Zhu, Zhu Zhu, Jiapeng Zhao, Yunan |
author_sort | Chen, Feiyan |
collection | PubMed |
description | BACKGROUND: Ginseng can help regulate brain excitability, promote learning and memory, and resist cerebral ischemia in the central nervous system. Ginsenosides are the major effective compounds of Ginseng, but their protein targets in the brain have not been determined. METHODS: We screened proteins that interact with the main components of ginseng (ginsenosides) by affinity chromatography and identified the 14-3-3 ζ protein as a potential target of ginsenosides in brain tissues. RESULTS: Biolayer interferometry (BLI) analysis showed that 20(S)-protopanaxadiol (PPD), a ginseng saponin metabolite, exhibited the highest direct interaction to the 14-3-3 ζ protein. Subsequently, BLI kinetics analysis and isothermal titration calorimetry (ITC) assay showed that PPD specifically bound to the 14-3-3 ζ protein. The cocrystal structure of the 14-3-3 ζ protein-PPD complex showed that the main interactions occurred between the residues R56, R127, and Y128 of the 14-3-3 ζ protein and a portion of PPD. Moreover, mutating any of the above residues resulted in a significant decrease of affinity between PPD and the 14-3-3 ζ protein. CONCLUSION: Our results indicate the 14-3-3 ζ protein is the target of PPD, a ginsenoside metabolite. Crystallographic and mutagenesis studies suggest a direct interaction between PPD and the 14-3-3 ζ protein. This finding can help in the development of small-molecular compounds that bind to the 14-3-3 ζ protein on the basis of the structure of dammarane-type triterpenoid. |
format | Online Article Text |
id | pubmed-8282492 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-82824922021-07-21 Identification and confirmation of 14-3-3 ζ as a novel target of ginsenosides in brain tissues Chen, Feiyan Chen, Lin Liang, Weifeng Zhang, Zhengguang Li, Jiao Zheng, Wan Zhu, Zhu Zhu, Jiapeng Zhao, Yunan J Ginseng Res Research Article BACKGROUND: Ginseng can help regulate brain excitability, promote learning and memory, and resist cerebral ischemia in the central nervous system. Ginsenosides are the major effective compounds of Ginseng, but their protein targets in the brain have not been determined. METHODS: We screened proteins that interact with the main components of ginseng (ginsenosides) by affinity chromatography and identified the 14-3-3 ζ protein as a potential target of ginsenosides in brain tissues. RESULTS: Biolayer interferometry (BLI) analysis showed that 20(S)-protopanaxadiol (PPD), a ginseng saponin metabolite, exhibited the highest direct interaction to the 14-3-3 ζ protein. Subsequently, BLI kinetics analysis and isothermal titration calorimetry (ITC) assay showed that PPD specifically bound to the 14-3-3 ζ protein. The cocrystal structure of the 14-3-3 ζ protein-PPD complex showed that the main interactions occurred between the residues R56, R127, and Y128 of the 14-3-3 ζ protein and a portion of PPD. Moreover, mutating any of the above residues resulted in a significant decrease of affinity between PPD and the 14-3-3 ζ protein. CONCLUSION: Our results indicate the 14-3-3 ζ protein is the target of PPD, a ginsenoside metabolite. Crystallographic and mutagenesis studies suggest a direct interaction between PPD and the 14-3-3 ζ protein. This finding can help in the development of small-molecular compounds that bind to the 14-3-3 ζ protein on the basis of the structure of dammarane-type triterpenoid. Elsevier 2021-07 2020-12-29 /pmc/articles/PMC8282492/ /pubmed/34295206 http://dx.doi.org/10.1016/j.jgr.2020.12.007 Text en © 2021 The Korean Society of Ginseng. Publishing services by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Article Chen, Feiyan Chen, Lin Liang, Weifeng Zhang, Zhengguang Li, Jiao Zheng, Wan Zhu, Zhu Zhu, Jiapeng Zhao, Yunan Identification and confirmation of 14-3-3 ζ as a novel target of ginsenosides in brain tissues |
title | Identification and confirmation of 14-3-3 ζ as a novel target of ginsenosides in brain tissues |
title_full | Identification and confirmation of 14-3-3 ζ as a novel target of ginsenosides in brain tissues |
title_fullStr | Identification and confirmation of 14-3-3 ζ as a novel target of ginsenosides in brain tissues |
title_full_unstemmed | Identification and confirmation of 14-3-3 ζ as a novel target of ginsenosides in brain tissues |
title_short | Identification and confirmation of 14-3-3 ζ as a novel target of ginsenosides in brain tissues |
title_sort | identification and confirmation of 14-3-3 ζ as a novel target of ginsenosides in brain tissues |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282492/ https://www.ncbi.nlm.nih.gov/pubmed/34295206 http://dx.doi.org/10.1016/j.jgr.2020.12.007 |
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