5FGH
Yeast 20S proteasome beta5-K33A mutant (propeptide expressed in trans) in complex with MG132
Summary for 5FGH
| Entry DOI | 10.2210/pdb5fgh/pdb |
| Related | 5CZ4 |
| Related PRD ID | PRD_001210 |
| 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, mutant, inhibitor, binding analysis, hydrolase/hydrolase inhibitor |
| Biological source | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) More |
| Total number of polymer chains | 28 |
| Total formula weight | 734136.64 |
| Authors | Huber, E.M.,Groll, M. (deposition date: 2015-12-20, release date: 2016-03-23, Last modification date: 2024-10-23) |
| Primary citation | Huber, E.M.,Heinemeyer, W.,Li, X.,Arendt, C.S.,Hochstrasser, M.,Groll, M. A unified mechanism for proteolysis and autocatalytic activation in the 20S proteasome. Nat Commun, 7:10900-10900, 2016 Cited by PubMed Abstract: Biogenesis of the 20S proteasome is tightly regulated. The N-terminal propeptides protecting the active-site threonines are autocatalytically released only on completion of assembly. However, the trigger for the self-activation and the reason for the strict conservation of threonine as the active site nucleophile remain enigmatic. Here we use mutagenesis, X-ray crystallography and biochemical assays to suggest that Lys33 initiates nucleophilic attack of the propeptide by deprotonating the Thr1 hydroxyl group and that both residues together with Asp17 are part of a catalytic triad. Substitution of Thr1 by Cys disrupts the interaction with Lys33 and inactivates the proteasome. Although a Thr1Ser mutant is active, it is less efficient compared with wild type because of the unfavourable orientation of Ser1 towards incoming substrates. This work provides insights into the basic mechanism of proteolysis and propeptide autolysis, as well as the evolutionary pressures that drove the proteasome to become a threonine protease. PubMed: 26964885DOI: 10.1038/ncomms10900 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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