5cz9

Yeast 20S proteasome beta5-D17N mutant in complex with Carfilzomib; Propeptide expressed in trans

spinqualitylabelsall models 5cz9, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5cz9 is a 20 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.9Å Ligands: 3BV, CL, MES, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PSA2_YEAST The proteasome degrades poly-ubiquitinated proteins in the cytoplasm and in the nucleus. It is essential for the regulated turnover of proteins and for the removal of misfolded proteins. The proteasome is a multicatalytic proteinase complex that is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. It has an ATP-dependent proteolytic activity. Publication Abstract from PubMed 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. A unified mechanism for proteolysis and autocatalytic activation in the 20S proteasome.,Huber EM, Heinemeyer W, Li X, Arendt CS, Hochstrasser M, Groll M Nat Commun. 2016 Mar 11;7:10900. doi: 10.1038/ncomms10900. PMID:26964885 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Proteasome 3D structures

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