| アイテムタイプ |
学術雑誌論文 = Journal Article(1) |
| 公開日 |
2024-05-08 |
| 資源タイプ |
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|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| タイトル |
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|
タイトル |
Computational Screening and Experimental Validation of Inhibitor Targeting the Complex Formation of Grb14 and Insulin Receptor |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| 著者 |
Ochi, Yosuke
Matsui, Takanori
Inoue, Keitaro
Monobe, Kohei
坂本, 寛
青木, 俊介
平, 順一
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| 抄録 |
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|
内容記述タイプ |
Abstract |
|
内容記述 |
The development of drugs targeting gene products associated with insulin resistance holds the potential to enhance our understanding of type 2 diabetes mellitus (T2DM). The virtual screening, based on a three-dimensional (3D) protein structure, is a potential technique to accelerate the development of molecular target drugs. Among the targets implicated in insulin resistance, the genetic characterization and protein function of Grb14 have been clarified without contradiction. The Grb14 gene displays significant variations in T2DM, and its gene product is known to inhibit the function of the insulin receptor (IR) by directly binding to the tyrosine kinase domain. In the present study, a virtual screening, based on a 3D structure of the IR tyrosine kinase domain (IRβ) in complex with part of Grb14, was conducted to find compounds that can disrupt the complex formation between Grb14 and IRβ. First, ten compounds were selected from 154,118 compounds via hierarchical in silico structure-based drug screening, composed of grid docking-based and genetic algorithm-based programs. The experimental validations suggested that the one compound can affect the blood glucose level. The molecular dynamics simulations and co-immunoprecipitation analysis showed that the compound did not completely suppress the protein–protein interaction between Grb14 and IR, though competitively bound to IR with the tyrosine kinase pseudosubstrate region in Grb14. |
|
言語 |
en |
| 書誌情報 |
en : Molecules
巻 29,
号 1,
p. 198,
発行日 2023-12-29
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| 出版社 |
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|
出版者 |
MDPI |
| DOI |
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関連タイプ |
isIdenticalTo |
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|
識別子タイプ |
DOI |
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|
関連識別子 |
https://doi.org/10.3390/molecules29010198 |
| ISSN |
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収録物識別子タイプ |
EISSN |
|
収録物識別子 |
1420-3049 |
| 著作権関連情報 |
|
|
権利情報Resource |
https://creativecommons.org/licenses/by/4.0/ |
|
権利情報 |
Copyright (c) 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
| キーワード |
|
|
主題Scheme |
Other |
|
主題 |
DOCK program |
| キーワード |
|
|
主題Scheme |
Other |
|
主題 |
GOLD program |
| キーワード |
|
|
主題Scheme |
Other |
|
主題 |
Grb14 |
| キーワード |
|
|
主題Scheme |
Other |
|
主題 |
insulin receptor (IR) |
| キーワード |
|
|
主題Scheme |
Other |
|
主題 |
structure-based drug screening (SBDS) |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| 査読の有無 |
|
|
値 |
yes |
| 研究者情報 |
|
|
URL |
https://hyokadb02.jimu.kyutech.ac.jp/html/282_ja.html |
| 論文ID（連携） |
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|
値 |
10430117 |
| 連携ID |
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|
値 |
12172 |
10430117.pdf (759 KB)
