5BOU
Yeast 20S proteasome in complex with a beta1 / beta2 specific non-peptidic sulfonamide Ligand
Summary for 5BOU
| Entry DOI | 10.2210/pdb5bou/pdb |
| Related | 1RYP |
| Descriptor | Proteasome subunit alpha type-2, Proteasome subunit beta type-4, Proteasome subunit beta type-5, ... (18 entities in total) |
| Functional Keywords | hydrolase-hydrolase inhibitor complex, proteasome, non-covalent ligand, binding analysis, hydrolase/hydrolase inhibitor |
| Biological source | Saccharomyces cerevisiae S288c (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 | 732295.20 |
| Authors | |
| Primary citation | Beck, P.,Reboud-Ravaux, M.,Groll, M. Identification of a beta 1/ beta 2-Specific Sulfonamide Proteasome Ligand by Crystallographic Screening. Angew.Chem.Int.Ed.Engl., 54:11275-11278, 2015 Cited by PubMed Abstract: The proteasome represents a validated drug target for the treatment of cancer, however, new types of inhibitors are required to tackle the development of resistant tumors. Current fluorescence-based screening methods suffer from low sensitivity and are limited to the detection of ligands with conventional binding profiles. In response to these drawbacks, a crystallographic screening procedure for the discovery of agents with a novel mode of action was utilized. The optimized workflow was applied to the screening of a focused set of compounds, resulting in the discovery of a β1/β2-specific sulfonamide derivative that noncovalently binds between subunits β1 and β2. The binding pocket displays significant differences in size and polarity between the immuno- and constitutive proteasome. The identified ligand thus provides valuable insights for the future structure-based design of subtype-specific proteasome inhibitors. PubMed: 26242779DOI: 10.1002/anie.201505054 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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