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Identification of Glycine Receptor α3 as a Colchicine-Binding Protein

Colchicine (Col) is considered a kind of highly effective alkaloid for preventing and treating acute gout attacks (flares). However, little is known about the underlying mechanism of Col in pain treatment. We have previously developed a customized virtual target identification method, termed IFPTarg...

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Autores principales: Zhou, Xikun, Wu, Mingbo, Xie, Yongmei, Li, Guo-Bo, Li, Tao, Xie, Rou, Wang, Kailun, Zhang, Yige, Zou, Chaoyu, Wu, Wenling, Wang, Qi, Wang, Xiangwei, Zhang, Ximu, Li, Jiong, Li, Jing, Wei, Yu-Quan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236057/
https://www.ncbi.nlm.nih.gov/pubmed/30467477
http://dx.doi.org/10.3389/fphar.2018.01238
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author Zhou, Xikun
Wu, Mingbo
Xie, Yongmei
Li, Guo-Bo
Li, Tao
Xie, Rou
Wang, Kailun
Zhang, Yige
Zou, Chaoyu
Wu, Wenling
Wang, Qi
Wang, Xiangwei
Zhang, Ximu
Li, Jiong
Li, Jing
Wei, Yu-Quan
author_facet Zhou, Xikun
Wu, Mingbo
Xie, Yongmei
Li, Guo-Bo
Li, Tao
Xie, Rou
Wang, Kailun
Zhang, Yige
Zou, Chaoyu
Wu, Wenling
Wang, Qi
Wang, Xiangwei
Zhang, Ximu
Li, Jiong
Li, Jing
Wei, Yu-Quan
author_sort Zhou, Xikun
collection PubMed
description Colchicine (Col) is considered a kind of highly effective alkaloid for preventing and treating acute gout attacks (flares). However, little is known about the underlying mechanism of Col in pain treatment. We have previously developed a customized virtual target identification method, termed IFPTarget, for small-molecule target identification. In this study, by using IFPTarget and ligand similarity ensemble approach (SEA), we show that the glycine receptor alpha 3 (GlyRα3), which play a key role in the processing of inflammatory pain, is a potential target of Col. Moreover, Col binds directly to the GlyRα3 as determined by the immunoprecipitation and bio-layer interferometry assays using the synthesized Col-biotin conjugate (linked Col and biotin with polyethylene glycol). These results suggest that GlyRα3 may mediate Col-induced suppression of inflammatory pain. However, whether GlyRα3 is the functional target of Col and serves as potential therapeutic target in gouty arthritis requires further investigations.
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spelling pubmed-62360572018-11-22 Identification of Glycine Receptor α3 as a Colchicine-Binding Protein Zhou, Xikun Wu, Mingbo Xie, Yongmei Li, Guo-Bo Li, Tao Xie, Rou Wang, Kailun Zhang, Yige Zou, Chaoyu Wu, Wenling Wang, Qi Wang, Xiangwei Zhang, Ximu Li, Jiong Li, Jing Wei, Yu-Quan Front Pharmacol Pharmacology Colchicine (Col) is considered a kind of highly effective alkaloid for preventing and treating acute gout attacks (flares). However, little is known about the underlying mechanism of Col in pain treatment. We have previously developed a customized virtual target identification method, termed IFPTarget, for small-molecule target identification. In this study, by using IFPTarget and ligand similarity ensemble approach (SEA), we show that the glycine receptor alpha 3 (GlyRα3), which play a key role in the processing of inflammatory pain, is a potential target of Col. Moreover, Col binds directly to the GlyRα3 as determined by the immunoprecipitation and bio-layer interferometry assays using the synthesized Col-biotin conjugate (linked Col and biotin with polyethylene glycol). These results suggest that GlyRα3 may mediate Col-induced suppression of inflammatory pain. However, whether GlyRα3 is the functional target of Col and serves as potential therapeutic target in gouty arthritis requires further investigations. Frontiers Media S.A. 2018-11-08 /pmc/articles/PMC6236057/ /pubmed/30467477 http://dx.doi.org/10.3389/fphar.2018.01238 Text en Copyright © 2018 Zhou, Wu, Xie, Li, Li, Xie, Wang, Zhang, Zou, Wu, Wang, Wang, Zhang, Li, Li and Wei. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Zhou, Xikun
Wu, Mingbo
Xie, Yongmei
Li, Guo-Bo
Li, Tao
Xie, Rou
Wang, Kailun
Zhang, Yige
Zou, Chaoyu
Wu, Wenling
Wang, Qi
Wang, Xiangwei
Zhang, Ximu
Li, Jiong
Li, Jing
Wei, Yu-Quan
Identification of Glycine Receptor α3 as a Colchicine-Binding Protein
title Identification of Glycine Receptor α3 as a Colchicine-Binding Protein
title_full Identification of Glycine Receptor α3 as a Colchicine-Binding Protein
title_fullStr Identification of Glycine Receptor α3 as a Colchicine-Binding Protein
title_full_unstemmed Identification of Glycine Receptor α3 as a Colchicine-Binding Protein
title_short Identification of Glycine Receptor α3 as a Colchicine-Binding Protein
title_sort identification of glycine receptor α3 as a colchicine-binding protein
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236057/
https://www.ncbi.nlm.nih.gov/pubmed/30467477
http://dx.doi.org/10.3389/fphar.2018.01238
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