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Journal Article
Research Support, Non-U.S. Gov't
Structural Elucidation of a Nonpeptidic Inhibitor Specific for the Human Immunoproteasome.
Chembiochem : a European Journal of Chemical Biology 2017 March 17
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 β5i substrate-binding channel. Distinct interactions between the inhibitor and the subpockets of the human immunoproteasome account for its isotype selectivity.
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