A strategy for modulation of enzymes in the ubiquitin system.

@article{Ernst2013ASF,
  title={A strategy for modulation of enzymes in the ubiquitin system.},
  author={Andreas Ernst and George V. Avvakumov and Jiefei Tong and Yihui Fan and Yanling Zhao and P. Sewes F. Alberts and Avinash D Persaud and John R. Walker and Ana-Mirela Neculai and Dante Neculai and Andrew Vorobyov and Pankaj Garg and Linda G. Beatty and Pak-Kei Chan and Yu-Chi Juang and Marie-Claude Landry and Christina Yeh and Elton Zeqiraj and Konstantina Karamboulas and Abdellah Allali-Hassani and Masoud Vedadi and Mike Tyers and Jason Moffat and Frank Sicheri and Laurence Pelletier and Daniel Durocher and Brian Raught and Daniela Rotin and Jianhua Yang and Michael F. Moran and Sirano dhe-Paganon and Sachdev S. Sidhu},
  journal={Science},
  year={2013},
  volume={339 6119},
  pages={
          590-5
        }
}
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… CONTINUE READING
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