Structural Elucidation of a Nonpeptidic Inhibitor Specific for the Human Immunoproteasome
| Autor: | Eva M. Huber, Michael Groll, Haissi Cui, Regina Baur, Camille Le Chapelain, Christian Dubiella, Wolfgang Heinemeyer |
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| Rok vydání: | 2017 |
| Předmět: |
Models
Molecular 0301 basic medicine Proteasome Endopeptidase Complex Molecular Structure Yeast Model Stereochemistry Organic Chemistry Selective inhibition Biochemistry 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology chemistry Electrophile Humans Immunologic Factors Molecular Medicine Peptides Thiazole Oligopeptides Proteasome Inhibitors Molecular Biology Lead compound |
| Zdroj: | ChemBioChem. 18:523-526 |
| ISSN: | 1439-4227 |
| Popis: | 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 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 β5i substrate binding channel. Distinctive interactions between the inhibitor and the subpockets of the human immunoproteasome account for its isotype selectivity. |
| Databáze: | OpenAIRE |
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