Molecular basis for the disruption of Keap1–Nrf2 interaction via Hinge & Latch mechanism

Using NMR spectroscopy, Horie, Suzuki, Inoue et al. show that the dissociation of Keap1 from Nrf2, or the Hinge-Latch mechanism, is triggered by Keap1-Nrf2 inhibitors and occurs during p62- mediated Nrf2 activation, but not by electrophilic Nrf2 inducers. This study provides insights into the design...

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Autores principales: Yuta Horie, Takafumi Suzuki, Jin Inoue, Tatsuro Iso, Geoffrey Wells, Terry W. Moore, Tsunehiro Mizushima, Albena T. Dinkova-Kostova, Takuma Kasai, Takashi Kamei, Seizo Koshiba, Masayuki Yamamoto
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/b744783a8c5b4f278122faa72d2167f4
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spelling oai:doaj.org-article:b744783a8c5b4f278122faa72d2167f42021-12-02T15:55:21ZMolecular basis for the disruption of Keap1–Nrf2 interaction via Hinge & Latch mechanism10.1038/s42003-021-02100-62399-3642https://doaj.org/article/b744783a8c5b4f278122faa72d2167f42021-05-01T00:00:00Zhttps://doi.org/10.1038/s42003-021-02100-6https://doaj.org/toc/2399-3642Using NMR spectroscopy, Horie, Suzuki, Inoue et al. show that the dissociation of Keap1 from Nrf2, or the Hinge-Latch mechanism, is triggered by Keap1-Nrf2 inhibitors and occurs during p62- mediated Nrf2 activation, but not by electrophilic Nrf2 inducers. This study provides insights into the design of Nrf2 activators targeting the Keap1-Nrf2 interaction.Yuta HorieTakafumi SuzukiJin InoueTatsuro IsoGeoffrey WellsTerry W. MooreTsunehiro MizushimaAlbena T. Dinkova-KostovaTakuma KasaiTakashi KameiSeizo KoshibaMasayuki YamamotoNature PortfolioarticleBiology (General)QH301-705.5ENCommunications Biology, Vol 4, Iss 1, Pp 1-11 (2021)
institution DOAJ
collection DOAJ
language EN
topic Biology (General)
QH301-705.5
spellingShingle Biology (General)
QH301-705.5
Yuta Horie
Takafumi Suzuki
Jin Inoue
Tatsuro Iso
Geoffrey Wells
Terry W. Moore
Tsunehiro Mizushima
Albena T. Dinkova-Kostova
Takuma Kasai
Takashi Kamei
Seizo Koshiba
Masayuki Yamamoto
Molecular basis for the disruption of Keap1–Nrf2 interaction via Hinge & Latch mechanism
description Using NMR spectroscopy, Horie, Suzuki, Inoue et al. show that the dissociation of Keap1 from Nrf2, or the Hinge-Latch mechanism, is triggered by Keap1-Nrf2 inhibitors and occurs during p62- mediated Nrf2 activation, but not by electrophilic Nrf2 inducers. This study provides insights into the design of Nrf2 activators targeting the Keap1-Nrf2 interaction.
format article
author Yuta Horie
Takafumi Suzuki
Jin Inoue
Tatsuro Iso
Geoffrey Wells
Terry W. Moore
Tsunehiro Mizushima
Albena T. Dinkova-Kostova
Takuma Kasai
Takashi Kamei
Seizo Koshiba
Masayuki Yamamoto
author_facet Yuta Horie
Takafumi Suzuki
Jin Inoue
Tatsuro Iso
Geoffrey Wells
Terry W. Moore
Tsunehiro Mizushima
Albena T. Dinkova-Kostova
Takuma Kasai
Takashi Kamei
Seizo Koshiba
Masayuki Yamamoto
author_sort Yuta Horie
title Molecular basis for the disruption of Keap1–Nrf2 interaction via Hinge & Latch mechanism
title_short Molecular basis for the disruption of Keap1–Nrf2 interaction via Hinge & Latch mechanism
title_full Molecular basis for the disruption of Keap1–Nrf2 interaction via Hinge & Latch mechanism
title_fullStr Molecular basis for the disruption of Keap1–Nrf2 interaction via Hinge & Latch mechanism
title_full_unstemmed Molecular basis for the disruption of Keap1–Nrf2 interaction via Hinge & Latch mechanism
title_sort molecular basis for the disruption of keap1–nrf2 interaction via hinge & latch mechanism
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/b744783a8c5b4f278122faa72d2167f4
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