3I3T

Crystal structure of covalent ubiquitin-USP21 complex

Summary for 3I3T

• Entry DOI: 10.2210/pdb3i3t/pdb
• Descriptor: Ubiquitin carboxyl-terminal hydrolase 21, Ubiquitin, ZINC ION, ... (5 entities in total)
• Functional Keywords: 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
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: Q9UK80
• Total number of polymer chains: 8
• Total formula weight: 194943.69

Authors

Neculai, D.,Avvakumov, G.V.,Walker, J.R.,Xue, S.,Butler-Cole, C.,Weigelt, J.,Bountra, C.,Edwards, A.M.,Arrowsmith, C.H.,Bochkarev, A.,Dhe-Paganon, S.,Structural Genomics Consortium (SGC) (deposition date: 2009-06-30, release date: 2009-07-21, 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 (2.59 Å)