3N3K

The catalytic domain of USP8 in complex with a USP8 specific inhibitor

3N3K の概要

• エントリーDOI: 10.2210/pdb3n3k/pdb
• 関連するPDBエントリー: 1WHB 2A9U 2FZP 2GFO
• 分子名称: Ubiquitin carboxyl-terminal hydrolase 8, Ubiquitin, ZINC ION, ... (4 entities in total)
• 機能のキーワード: hydrolase, protease, thiol protease, ubl conjugation pathway, deubiquitinating enzyme, dub, zinc ribbon, inhibitor, ubiquitin, isopeptide bond, nucleus, phosphoprotein, structural genomics, structural genomics consortium, sgc
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm : P40818
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 54751.48

構造登録者

Walker, J.R.,Avvakumov, G.V.,Xue, S.,Li, Y.,Allali-Hassani, A.,Lam, R.,Ernst, A.,Sidhu, S.,Weigelt, J.,Bountra, C.,Arrowsmith, C.H.,Edwards, A.M.,Bochkarev, A.,Dhe-Paganon, S.,Structural Genomics Consortium (SGC) (登録日: 2010-05-20, 公開日: 2010-06-23, 最終更新日: 2025-10-22)

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 (2.6 Å)