3MTN

Usp21 in complex with a ubiquitin-based, USP21-specific inhibitor

3MTN の概要

• エントリーDOI: 10.2210/pdb3mtn/pdb
• 関連するPDBエントリー: 3I3T
• 分子名称: Ubiquitin carboxyl-terminal hydrolase 21, UBIQUITIN VARIANT UBV.21.4, ZINC ION, ... (6 entities in total)
• 機能のキーワード: ubiquitin-specific protease activity, hydrolase, ubiquitin biology, structural genomics consortium, sgc, activator, chromatin regulator, nucleus, protease, thiol protease, transcription, transcription regulation, ubl conjugation pathway, isopeptide bond, phosphoprotein, inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: Q9UK80
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 103043.34

構造登録者

Walker, J.R.,Avvakumov, G.V.,Xue, S.,Li, Y.,Ernst, A.,Sidhu, S.,Weigelt, J.,Bountra, C.,Edwards, A.M.,Arrowsmith, C.H.,Bochkarev, A.,Dhe-Paganon, S.,Structural Genomics Consortium (SGC) (登録日: 2010-04-30, 公開日: 2010-06-09, 最終更新日: 2023-09-06)

主引用文献

Ernst, A.,Avvakumov, G.,Tong, J.,Fan, Y.,Zhao, Y.,Alberts, P.,Persaud, A.,Walker, J.R.,Neculai, A.M.,Neculai, D.,Vorobyov, A.,Garg, P.,Beatty, L.,Chan, P.K.,Juang, Y.C.,Landry, M.C.,Yeh, C.,Zeqiraj, E.,Karamboulas, K.,Allali-Hassani, A.,Vedadi, M.,Tyers, M.,Moffat, J.,Sicheri, F.,Pelletier, L.,Durocher, D.,Raught, B.,Rotin, D.,Yang, J.,Moran, M.F.,Dhe-Paganon, S.,Sidhu, S.S.
A strategy for modulation of enzymes in the ubiquitin system.
Science, 339:590-595, 2013

PubMed Abstract: The ubiquitin system regulates virtually all aspects of cellular function. We report a method to target the myriad enzymes that govern ubiquitination of protein substrates. We used massively diverse combinatorial libraries of ubiquitin variants to develop inhibitors of four deubiquitinases (DUBs) and analyzed the DUB-inhibitor complexes with crystallography. We extended the selection strategy to the ubiquitin conjugating (E2) and ubiquitin ligase (E3) enzymes and found that ubiquitin variants can also enhance enzyme activity. Last, we showed that ubiquitin variants can bind selectively to ubiquitin-binding domains. Ubiquitin variants exhibit selective function in cells and thus enable orthogonal modulation of specific enzymatic steps in the ubiquitin system.

PubMed: 23287719
DOI: 10.1126/science.1230161

実験手法

X-RAY DIFFRACTION (2.7 Å)