8P0T
CryoEM structure of 20S Trichomonas vaginalis proteasome in complex with proteasome inhibitor CP-17
Summary for 8P0T
| Entry DOI | 10.2210/pdb8p0t/pdb |
| Related | 8OIX |
| EMDB information | 17337 |
| Descriptor | Family T1, proteasome alpha subunit, threonine peptidase, Proteasome subunit beta, Family T1, proteasome beta subunit, threonine peptidase, ... (15 entities in total) |
| Functional Keywords | proteasome, 20s, trichomonas vaginalis, covalently bound protease inhibitor cp-17, hydrolase |
| Biological source | Trichomonas vaginalis G3 More |
| Total number of polymer chains | 28 |
| Total formula weight | 709991.77 |
| Authors | Silhan, J.,Boura, E.,Fajtova, P. (deposition date: 2023-05-10, release date: 2024-05-22, Last modification date: 2024-11-20) |
| Primary citation | Silhan, J.,Fajtova, P.,Bartosova, J.,Hurysz, B.M.,Almaliti, J.,Miyamoto, Y.,Eckmann, L.,Gerwick, W.H.,O'Donoghue, A.J.,Boura, E. Structural elucidation of recombinant Trichomonas vaginalis 20S proteasome bound to covalent inhibitors. Nat Commun, 15:8621-8621, 2024 Cited by PubMed Abstract: The proteasome is a proteolytic enzyme complex essential for protein homeostasis in mammalian cells and protozoan parasites like Trichomonas vaginalis (Tv), the cause of the most common, non-viral sexually transmitted disease. Tv and other protozoan 20S proteasomes have been validated as druggable targets for antimicrobials. However, low yields and purity of the native proteasome have hindered studies of the Tv 20S proteasome (Tv20S). We address this challenge by creating a recombinant protozoan proteasome by expressing all seven α and seven β subunits of Tv20S alongside the Ump-1 chaperone in insect cells. The recombinant Tv20S displays biochemical equivalence to its native counterpart, confirmed by various assays. Notably, the marizomib (MZB) inhibits all catalytic subunits of Tv20S, while the peptide inhibitor carmaphycin-17 (CP-17) specifically targets β2 and β5. Cryo-electron microscopy (cryo-EM) unveils the structures of Tv20S bound to MZB and CP-17 at 2.8 Å. These findings explain MZB's low specificity for Tv20S compared to the human proteasome and demonstrate CP-17's higher specificity. Overall, these data provide a structure-based strategy for the development of specific Tv20S inhibitors to treat trichomoniasis. PubMed: 39366995DOI: 10.1038/s41467-024-53022-w PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.65 Å) |
Structure validation
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