Journal
CHEMBIOCHEM
Volume 18, Issue 6, Pages 523-526Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201700021
Keywords
crystallography; drug design; immunoproteasome; inhibitors; specificity
Funding
- [SFB 1035/A2]
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Selective inhibition of the immunoproteasome is a promising approach towards the development of immunomodulatory drugs. Recently, a class of substituted thiazole compounds that combine a nonpeptidic scaffold with the absence of an electrophile was reported in a patent. Here, we investigated the mode of action of the lead compound by using a sophisticated chimeric yeast model of the human immunoproteasome for structural studies. The inhibitor adopts a unique orientation perpendicular to the 5i substrate-binding channel. Distinct interactions between the inhibitor and the subpockets of the human immunoproteasome account for its isotype selectivity.
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