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8YVP

canine immunoproteasome 20S subunit in complex with compound 1

これはPDB形式変換不可エントリーです。
8YVP の概要
エントリーDOI10.2210/pdb8yvp/pdb
EMDBエントリー39612
分子名称Proteasome subunit beta type-7, Proteasome subunit alpha type-5, Proteasome subunit beta type-2, ... (16 entities in total)
機能のキーワードinhibitor, complex, proteasome, hydrolase
由来する生物種Mus musculus (house mouse)
詳細
タンパク質・核酸の鎖数28
化学式量合計735360.49
構造登録者
Kashima, A.,Arai, Y. (登録日: 2024-03-29, 公開日: 2024-07-31, 最終更新日: 2024-10-30)
主引用文献Arai, Y.,Shitama, H.,Yamagishi, M.,Ono, S.,Kashima, A.,Hiraizumi, M.,Tsuda, N.,Katayama, K.,Tanaka, K.,Koda, Y.,Kato, S.,Sakata, K.,Nureki, O.,Miyazaki, H.
Optimization of alpha-amido boronic acids via cryo-electron microscopy analysis: Discovery of a novel highly selective immunoproteasome subunit LMP7 ( beta 5i)/LMP2 ( beta 1i) dual inhibitor.
Bioorg.Med.Chem., 109:117790-117790, 2024
Cited by
PubMed Abstract: The immunoproteasome subunit LMP7 (β5i)/LMP2 (β1i) dual blockade has been reported to suppress B cell differentiation and activation, suggesting that the dual inhibition of LMP7/LMP2 is a promising approach for treating autoimmune diseases. In contrast, the inhibition of the constitutive proteasome subunit β5c correlates with cytotoxicity against non-immune cells. Therefore, LMP7/LMP2 dual inhibitors with high selectivity over β5c may be desirable for treating autoimmune diseases. In this study, we present the optimization and discovery of α-amido boronic acids using cryo-electron microscopy (cryo-EM). The exploitation of structural differences between the proteasome subunits led to the identification of a highly selective LMP7/LMP2 dual inhibitor 19. Molecular dynamics simulation based on cryo-EM structures of the proteasome subunits complexed with 19 explained the inhibitory activity profile. In mice immunized with 4-hydroxy-3-nitrophenylacetyl conjugated to ovalbumin, results indicate that 19 is orally bioavailable and shows promise as potential treatment for autoimmune diseases.
PubMed: 38906067
DOI: 10.1016/j.bmc.2024.117790
主引用文献が同じPDBエントリー
実験手法
ELECTRON MICROSCOPY (2.5 Å)
構造検証レポート
Validation report summary of 8yvp
検証レポート(詳細版)ダウンロードをダウンロード

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件を2025-05-28に公開中

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