3un4

Yeast 20S proteasome in complex with PR-957 (morpholine)Yeast 20S proteasome in complex with PR-957 (morpholine)

Structural highlights 3un4 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 3.4Å Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PSB5_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. This unit is responsible of the chymotrypsin-like activity of the proteasome and is one of the principal target of the proteasome inhibitor bortezomib. This subunit is necessary for chymotryptic activity and degradation of ubiquitinated proteins. Publication Abstract from PubMed Constitutive proteasomes and immunoproteasomes shape the peptide repertoire presented by major histocompatibility complex class I (MHC-I) molecules by harboring different sets of catalytically active subunits. Here, we present the crystal structures of constitutive proteasomes and immunoproteasomes from mouse in the presence and absence of the epoxyketone inhibitor PR-957 (ONX 0914) at 2.9 A resolution. Based on our X-ray data, we propose a unique catalytic feature for the immunoproteasome subunit beta5i/LMP7. Comparison of ligand-free and ligand-bound proteasomes reveals conformational changes in the S1 pocket of beta5c/X but not beta5i, thereby explaining the selectivity of PR-957 for beta5i. Time-resolved structures of yeast proteasome:PR-957 complexes indicate that ligand docking to the active site occurs only via the reactive head group and the P1 side chain. Together, our results support structure-guided design of inhibitory lead structures selective for immunoproteasomes that are linked to cytokine production and diseases like cancer and autoimmune disorders. Immuno- and constitutive proteasome crystal structures reveal differences in substrate and inhibitor specificity.,Huber EM, Basler M, Schwab R, Heinemeyer W, Kirk CJ, Groettrup M, Groll M Cell. 2012 Feb 17;148(4):727-38. PMID:22341445 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Proteasome 3D structures

spinqualitylabelsall models 3un4, resolution 3.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image