3N3K

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

Summary for 3N3K

• Entry DOI: 10.2210/pdb3n3k/pdb
• Related: 1WHB 2A9U 2FZP 2GFO
• Descriptor: Ubiquitin carboxyl-terminal hydrolase 8, Ubiquitin, ZINC ION, ... (4 entities in total)
• Functional Keywords: hydrolase, protease, thiol protease, ubl conjugation pathway, deubiquitinating enzyme, dub, zinc ribbon, inhibitor, ubiquitin, isopeptide bond, nucleus, phosphoprotein, structural genomics, structural genomics consortium, sgc
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm : P40818
• Total number of polymer chains: 2
• Total formula weight: 54751.48

Authors

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,Structural Genomics Consortium (SGC) (deposition date: 2010-05-20, release date: 2010-06-23, Last modification date: 2023-09-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.6 Å)