Structural highlights
FunctionPSA2_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 PubMedSelective inhibition of the immunoproteasome is a promising approach towards the development of immunomodulatory drugs. Recently, a class of substituted thiazole compounds that combine a non-peptidic scaffold with the absence of an electrophile has been reported in a patent. Herein, we describe the mode of action of the lead compound using a sophisticated chimeric yeast model of the human immunoproteasome for structural studies. The inhibitor adopts a unique orientation perpendicular to the beta5i substrate binding channel. Distinctive interactions between the inhibitor and the subpockets of the human immunoproteasome account for its isotype selectivity. Structural elucidation of a non-peptidic inhibitor specific for the human immunoproteasome.,Cui H, Baur R, Le Chapelain C, Dubiella C, Heinemeyer W, Huber EM, Groll M Chembiochem. 2017 Jan 18. doi: 10.1002/cbic.201700021. PMID:28098422[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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