ArticleThe EMBO journal2016
A humanized yeast proteasome identifies unique binding modes of inhibitors for the immunosubunit β5i.
Article in The EMBO journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Trends on Potential Boron-containing Drugs by Advancements in Ligand-protein Crystals Complexes.Current medicinal chemistry · 2025Review
- Humanization reveals pervasive incompatibility of yeast and human kinetochore components.G3 (Bethesda, Md.) · 2023Article
- Species-specific protein-protein interactions govern the humanization of the 20S proteasome in yeast.Genetics · 2023Article
- Structure of the reduced microsporidian proteasome bound by PI31-like peptides in dormant spores.Nature communications · 2022Article
- Site-Specific Proteasome Inhibitors.Biomolecules · 2021Review
- Article
- M3258 Is a Selective Inhibitor of the Immunoproteasome Subunit LMP7 (β5i) Delivering Efficacy in Multiple Myeloma Models.Molecular cancer therapeutics · 2021Article
- A Nut for Every Bolt: Subunit-Selective Inhibitors of the Immunoproteasome and Their Therapeutic Potential.Cells · 2021Review
- Characterization of Fully Recombinant Human 20S and 20S-PA200 Proteasome Complexes.Molecular cell · 2019Article
- Engineering Forward Genetics into Cultured Cancer Cells for Chemical Target Identification.Cell chemical biology · 2019Article
- Discovery of Immunoproteasome Inhibitors Using Large-Scale Covalent Virtual Screening.Molecules (Basel, Switzerland) · 2019Article
- Structure-Based Design of Inhibitors Selective for Human Proteasome β2c or β2i Subunits.Journal of medicinal chemistry · 2019Article
- Amelioration of autoimmunity with an inhibitor selectively targeting all active centres of the immunoproteasome.British journal of pharmacology · 2018Article
- High-resolution cryo-EM proteasome structures in drug development.Acta crystallographica. Section D, Structural biology · 2017Article
- Structural Basis for the Species-Selective Binding of N,C-Capped Dipeptides to the Mycobacterium tuberculosis Proteasome.Biochemistry · 2017Article
- A humanized yeast proteasome identifies unique binding modes of inhibitors for the immunosubunit β5i.The EMBO journal · 2016Article
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5 authors.
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Abstract
Inhibition of the immunoproteasome subunit β5i alleviates autoimmune diseases in preclinical studies and represents a promising new anti-inflammatory therapy. However, the lack of structural data on the human immunoproteasome still hampers drug design. Here, we systematically determined the potency of seven α' β' epoxyketone inhibitors with varying N-caps and P3-stereochemistry for mouse/human β5c/β5i and found pronounced differences in their subunit and species selectivity. Using X-ray crystallography, the compounds were analyzed for their modes of binding to chimeric yeast proteasomes that incorporate key parts of human β5c, human β5i or mouse β5i and the neighboring β6 subunit. The structural data reveal exceptional conformations for the most selective human β5i inhibitors and highlight subtle structural differences as the major reason for the observed species selectivity. Altogether, the presented results validate the humanized yeast proteasome as a powerful tool for structure-based development of β5i inhibitors with potential clinical applications.
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