Item type |
文献 / Documents(1) |
公開日 |
2019-02-26 |
アクセス権 |
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アクセス権 |
open access |
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 |
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資源タイプ |
journal article |
出版社版DOI |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1038/s42004-019-0118-3 |
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言語 |
ja |
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関連名称 |
10.1038/s42004-019-0118-3 |
出版タイプ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
タイトル |
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タイトル |
Natural ligand-nonmimetic inhibitors of the lipid-transfer protein CERT |
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言語 |
en |
著者 |
ナカオ, ナオキ
上野, 雅晴
サカイ, ショウタ
エガワ, ダイチ
ハンザワ, ヒロユキ
カワサキ, ショウヘイ
クマガイ, ケイゴ
スズキ, マコト
コバヤシ, シュウ
ハナダ, ケンタロウ
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抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Lipid transfer proteins mediate inter-organelle transport of membrane lipids at organelle contact sites in cells, playing fundamental roles in the lipidome and membrane biogenesis in eukaryotes. We previously developed a ceramide-mimetic compound as a potent inhibitor of the ceramide transport protein CERT. Here we develop CERT inhibitors with structures unrelated to ceramide. To this aim, we identify a seed compound with no ceramide-like structure but with the capability of forming a hydrogen-bonding network in the ceramide-binding START domain, by virtual screening of ~3 × 106 compounds. We also establish a surface plasmon resonance-based system to directly determine the affinity of compounds for the START domain. Then, we subject the seed compound to a series of in silico docking simulations, efficient chemical synthesis, affinity analysis, protein-ligand co-crystallography, and various in vivo assays. This strategy allows us to obtain ceramide-unrelated compounds that potently inhibited the function of CERT in human cultured cells. |
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言語 |
en |
書誌情報 |
en : Communications Chemistry
巻 2,
p. 20,
発行日 2019-02-20
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収録物ID |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
23993669 |
出版者 |
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出版者 |
Springer Nature |
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言語 |
en |
権利情報 |
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言語 |
en |
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権利情報 |
© 2019 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
EID |
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識別子 |
349539 |
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識別子タイプ |
URI |
言語 |
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言語 |
eng |