3UN4
Yeast 20S proteasome in complex with PR-957 (morpholine)
Summary for 3UN4
| Entry DOI | 10.2210/pdb3un4/pdb |
| Related | 1IRU 1PMA 1RYP 3UN8 3UNB 3UNE 3UNF 3UNH |
| Related PRD ID | PRD_000991 |
| Descriptor | Proteasome component Y7, Proteasome component C11, Proteasome component PRE2, ... (16 entities in total) |
| Functional Keywords | proteasome, antigen presentation, drug development, protein degradation, hydrolase -hydrolase-inhibitor complex, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Saccharomyces cerevisiae (Baker's yeast) More |
| Cellular location | Cytoplasm: P23639 P22141 P30656 P23724 P30657 P38624 P23638 P40303 P32379 P40302 P21242 P21243 P25043 P25451 |
| Total number of polymer chains | 28 |
| Total formula weight | 732048.20 |
| Authors | Huber, E.,Basler, M.,Schwab, R.,Heinemeyer, W.,Kirk, C.,Groettrup, M.,Groll, M. (deposition date: 2011-11-15, release date: 2012-02-29, Last modification date: 2024-11-20) |
| Primary citation | Huber, E.M.,Basler, M.,Schwab, R.,Heinemeyer, W.,Kirk, C.J.,Groettrup, M.,Groll, M. Immuno- and constitutive proteasome crystal structures reveal differences in substrate and inhibitor specificity. Cell(Cambridge,Mass.), 148:727-738, 2012 Cited by PubMed Abstract: Constitutive proteasomes and immunoproteasomes shape the peptide repertoire presented by major histocompatibility complex class I (MHC-I) molecules by harboring different sets of catalytically active subunits. Here, we present the crystal structures of constitutive proteasomes and immunoproteasomes from mouse in the presence and absence of the epoxyketone inhibitor PR-957 (ONX 0914) at 2.9 Å resolution. Based on our X-ray data, we propose a unique catalytic feature for the immunoproteasome subunit β5i/LMP7. Comparison of ligand-free and ligand-bound proteasomes reveals conformational changes in the S1 pocket of β5c/X but not β5i, thereby explaining the selectivity of PR-957 for β5i. Time-resolved structures of yeast proteasome:PR-957 complexes indicate that ligand docking to the active site occurs only via the reactive head group and the P1 side chain. Together, our results support structure-guided design of inhibitory lead structures selective for immunoproteasomes that are linked to cytokine production and diseases like cancer and autoimmune disorders. PubMed: 22341445DOI: 10.1016/j.cell.2011.12.030 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.4 Å) |
Structure validation
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