Summary for 5NIF
| Entry DOI | 10.2210/pdb5nif/pdb |
| Descriptor | Proteasome subunit alpha type-1, Proteasome subunit beta type-3, Proteasome subunit beta type-4, ... (20 entities in total) |
| Functional Keywords | 20s proteasome, low-molecular mass activators, allosteric regulation, hydrolase |
| Biological source | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) More |
| Cellular location | Cytoplasm : P21243 P25451 P22141 P30656 P23724 P30657 P23639 P23638 P40303 P32379 P40302 P21242 P38624 P25043 |
| Total number of polymer chains | 30 |
| Total formula weight | 772611.80 |
| Authors | Witkowska, J.,Grudnik, P.,Golik, P.,Dubin, G.,Jankowska, E. (deposition date: 2017-03-23, release date: 2017-08-02, Last modification date: 2024-01-17) |
| Primary citation | Witkowska, J.,Gizynska, M.,Grudnik, P.,Golik, P.,Karpowicz, P.,Giedon, A.,Dubin, G.,Jankowska, E. Crystal structure of a low molecular weight activator Blm-pep with yeast 20S proteasome - insights into the enzyme activation mechanism. Sci Rep, 7:6177-6177, 2017 Cited by PubMed Abstract: Proteasomes are responsible for protein turnover in eukaryotic cells, degrading short-lived species but also removing improperly folded or oxidatively damaged ones. Dysfunction of a proteasome results in gradual accumulation of misfolded/damaged proteins, leading to their aggregation. It has been postulated that proteasome activators may facilitate removal of such aggregation-prone proteins and thus prevent development of neurodegenerative disorders. However, the discovery of pharmacologically relevant compounds is hindered by insufficient structural understanding of the activation process. In this study we provide a model peptidic activator of human proteasome and analyze the structure-activity relationship within this novel scaffold. The binding mode of the activator at the relevant pocket within the proteasome has been determined by X-ray crystallography. This crystal structure provides an important basis for rational design of pharmacological compounds. Moreover, by providing a novel insight into the proteasome gating mechanism, our results allow the commonly accepted model of proteasome regulation to be revisited. PubMed: 28733623DOI: 10.1038/s41598-017-05997-4 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3 Å) |
Structure validation
Download full validation report
