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Interaction and Inhibition of a Ganoderma lucidum Proteoglycan on PTP1B Activity for Anti-diabetes

[Image: see text] Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin and an effective target for the treatment of type 2 diabetes (T2D). A natural hyperbranched proteoglycan extracted from Ganoderma lucidum, namely, Fudan-Yueyang G. Lucidum (FYGL), was demonstrated capabl...

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Autores principales: Yu, Fanzhen, Wang, Yingxin, Teng, Yilong, Yang, Shutong, He, Yanming, Zhang, Zeng, Yang, Hongjie, Ding, Chuan-Fan, Zhou, Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582033/
https://www.ncbi.nlm.nih.gov/pubmed/34778653
http://dx.doi.org/10.1021/acsomega.1c04244
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author Yu, Fanzhen
Wang, Yingxin
Teng, Yilong
Yang, Shutong
He, Yanming
Zhang, Zeng
Yang, Hongjie
Ding, Chuan-Fan
Zhou, Ping
author_facet Yu, Fanzhen
Wang, Yingxin
Teng, Yilong
Yang, Shutong
He, Yanming
Zhang, Zeng
Yang, Hongjie
Ding, Chuan-Fan
Zhou, Ping
author_sort Yu, Fanzhen
collection PubMed
description [Image: see text] Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin and an effective target for the treatment of type 2 diabetes (T2D). A natural hyperbranched proteoglycan extracted from Ganoderma lucidum, namely, Fudan-Yueyang G. Lucidum (FYGL), was demonstrated capable of inhibiting the activity of PTP1B. Here, to identify the effective active components of FYGL, three different components, the polysaccharide FYGL-1, proteoglycans FYGL-2, and FYGL-3, were isolated from FYGL, and then, the protein moiety of FYGL-3 was further separated, namely, FYGL-3-P. Their abilities to enhance the glucose uptake in cells and inhibit the activity of PTP1B were compared. The inhibitory mechanisms were systematically explored by spectroscopic methods and MD simulations. The results showed that FYGL-3 and FYGL-3-P significantly enhanced the insulin-provoked glucose uptake in insulin-resistant HepG2 cells, detected by the glucose oxidase method. Also, the FYGL-3-P protein moiety in FYGL played an essential role in inhibiting the activity of PTP1B. A strong, enthalpy-driven, and multitargeted interaction by electrostatic forces between PTP1B and FYGL-3-P dramatically inhibited the catalytic activity of PTP1B. These results provided deep insights into the molecular mechanisms of FYGL inhibiting the activity of PTP1B and structurally helped researchers seek natural PTP1B inhibitors.
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spelling pubmed-85820332021-11-12 Interaction and Inhibition of a Ganoderma lucidum Proteoglycan on PTP1B Activity for Anti-diabetes Yu, Fanzhen Wang, Yingxin Teng, Yilong Yang, Shutong He, Yanming Zhang, Zeng Yang, Hongjie Ding, Chuan-Fan Zhou, Ping ACS Omega [Image: see text] Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin and an effective target for the treatment of type 2 diabetes (T2D). A natural hyperbranched proteoglycan extracted from Ganoderma lucidum, namely, Fudan-Yueyang G. Lucidum (FYGL), was demonstrated capable of inhibiting the activity of PTP1B. Here, to identify the effective active components of FYGL, three different components, the polysaccharide FYGL-1, proteoglycans FYGL-2, and FYGL-3, were isolated from FYGL, and then, the protein moiety of FYGL-3 was further separated, namely, FYGL-3-P. Their abilities to enhance the glucose uptake in cells and inhibit the activity of PTP1B were compared. The inhibitory mechanisms were systematically explored by spectroscopic methods and MD simulations. The results showed that FYGL-3 and FYGL-3-P significantly enhanced the insulin-provoked glucose uptake in insulin-resistant HepG2 cells, detected by the glucose oxidase method. Also, the FYGL-3-P protein moiety in FYGL played an essential role in inhibiting the activity of PTP1B. A strong, enthalpy-driven, and multitargeted interaction by electrostatic forces between PTP1B and FYGL-3-P dramatically inhibited the catalytic activity of PTP1B. These results provided deep insights into the molecular mechanisms of FYGL inhibiting the activity of PTP1B and structurally helped researchers seek natural PTP1B inhibitors. American Chemical Society 2021-10-27 /pmc/articles/PMC8582033/ /pubmed/34778653 http://dx.doi.org/10.1021/acsomega.1c04244 Text en © 2021 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Yu, Fanzhen
Wang, Yingxin
Teng, Yilong
Yang, Shutong
He, Yanming
Zhang, Zeng
Yang, Hongjie
Ding, Chuan-Fan
Zhou, Ping
Interaction and Inhibition of a Ganoderma lucidum Proteoglycan on PTP1B Activity for Anti-diabetes
title Interaction and Inhibition of a Ganoderma lucidum Proteoglycan on PTP1B Activity for Anti-diabetes
title_full Interaction and Inhibition of a Ganoderma lucidum Proteoglycan on PTP1B Activity for Anti-diabetes
title_fullStr Interaction and Inhibition of a Ganoderma lucidum Proteoglycan on PTP1B Activity for Anti-diabetes
title_full_unstemmed Interaction and Inhibition of a Ganoderma lucidum Proteoglycan on PTP1B Activity for Anti-diabetes
title_short Interaction and Inhibition of a Ganoderma lucidum Proteoglycan on PTP1B Activity for Anti-diabetes
title_sort interaction and inhibition of a ganoderma lucidum proteoglycan on ptp1b activity for anti-diabetes
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582033/
https://www.ncbi.nlm.nih.gov/pubmed/34778653
http://dx.doi.org/10.1021/acsomega.1c04244
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