Structural highlights
Function
PSA6_YEAST The proteasome degrades poly-ubiquitinated proteins in the cytoplasm and in the nucleus. It is essential for the regulated turnover of proteins and for the removal of misfolded proteins. The proteasome is a multicatalytic proteinase complex that is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. It has an ATP-dependent proteolytic activity.
Publication Abstract from PubMed
The concept of proteasome inhibition ranks among the latest achievements in the treatment of blood cancer and represents a promising strategy for modulating autoimmune diseases. In this study, we describe peptidic sulfonyl fluoride inhibitors that selectively block the catalytic beta5 subunit of the immunoproteasome by inducing only marginal cytotoxic effects. Structural and mass spectrometric analyses revealed a novel reaction mechanism involving polarity inversion and irreversible crosslinking of the proteasomal active site. We thus identified the sulfonyl fluoride headgroup for the development and optimization of immunoproteasome selective compounds and their possible application in autoimmune disorders.
Selective Inhibition of the Immunoproteasome by Ligand-Induced Crosslinking of the Active Site.,Dubiella C, Cui H, Gersch M, Brouwer AJ, Sieber SA, Kruger A, Liskamp RM, Groll M Angew Chem Int Ed Engl. 2014 Sep 22. doi: 10.1002/anie.201406964. PMID:25244435[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Dubiella C, Cui H, Gersch M, Brouwer AJ, Sieber SA, Kruger A, Liskamp RM, Groll M. Selective Inhibition of the Immunoproteasome by Ligand-Induced Crosslinking of the Active Site. Angew Chem Int Ed Engl. 2014 Sep 22. doi: 10.1002/anie.201406964. PMID:25244435 doi:http://dx.doi.org/10.1002/anie.201406964
