5l5z

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'''Unreleased structure'''
 
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The entry 5l5z is ON HOLD until Paper Publication
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==Yeast 20S proteasome with human beta5c (1-138) and human beta6 (97-111; 118-133) in complex with bortezomib==
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<StructureSection load='5l5z' size='340' side='right'caption='[[5l5z]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[5l5z]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5L5Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5L5Z FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BO2:N-[(1R)-1-(DIHYDROXYBORYL)-3-METHYLBUTYL]-N-(PYRAZIN-2-YLCARBONYL)-L-PHENYLALANINAMIDE'>BO2</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5l5z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l5z OCA], [https://pdbe.org/5l5z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5l5z RCSB], [https://www.ebi.ac.uk/pdbsum/5l5z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5l5z ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PSB5_YEAST 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.[https://www.uniprot.org/uniprot/PSB5_HUMAN PSB5_HUMAN] The proteasome is a multicatalytic proteinase complex which 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. The proteasome 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. May catalyze basal processing of intracellular antigens. Plays a role in the protection against oxidative damage through the Nrf2-ARE pathway (By similarity).
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Inhibition of the immunoproteasome subunit beta5i alleviates autoimmune diseases in preclinical studies and represents a promising new anti-inflammatory therapy. However, the lack of structural data on the human immunoproteasome still hampers drug design. Here, we systematically determined the potency of seven alpha' beta' epoxyketone inhibitors with varying N-caps and P3-stereochemistry for mouse/human beta5c/beta5i and found pronounced differences in their subunit and species selectivity. Using X-ray crystallography, the compounds were analyzed for their modes of binding to chimeric yeast proteasomes that incorporate key parts of human beta5c, human beta5i or mouse beta5i and the neighboring beta6 subunit. The structural data reveal exceptional conformations for the most selective human beta5i inhibitors and highlight subtle structural differences as the major reason for the observed species selectivity. Altogether, the presented results validate the humanized yeast proteasome as a powerful tool for structure-based development of beta5i inhibitors with potential clinical applications.
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Authors: Groll, M., Huber, E.M.
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A humanized yeast proteasome identifies unique binding modes of inhibitors for the immunosubunit beta5i.,Huber EM, Heinemeyer W, de Bruin G, Overkleeft HS, Groll M EMBO J. 2016 Dec 1;35(23):2602-2613. Epub 2016 Oct 27. PMID:27789522<ref>PMID:27789522</ref>
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Description: Yeast 20S proteasome with human beta5c (1-138) and human beta6 (97-111; 118-133) in complex with bortezomib
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Huber, E.M]]
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<div class="pdbe-citations 5l5z" style="background-color:#fffaf0;"></div>
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[[Category: Groll, M]]
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==See Also==
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*[[Proteasome 3D structures|Proteasome 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Saccharomyces cerevisiae S288C]]
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[[Category: Groll M]]
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[[Category: Huber EM]]

Current revision

Yeast 20S proteasome with human beta5c (1-138) and human beta6 (97-111; 118-133) in complex with bortezomib

PDB ID 5l5z

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