9s78
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Yeast 20S Proteasome in Complex with Tellurophene-Tagged Carfilzomib== | |
| + | <StructureSection load='9s78' size='340' side='right'caption='[[9s78]], [[Resolution|resolution]] 3.15Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9s78]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9S78 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9S78 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.15Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=00E:MORPHOLIN-4-YLACETIC+ACID'>00E</scene>, <scene name='pdbligand=A1I67:(2~{R},3~{S},6~{R},7~{S})-7-[(1~{S})-1-azanyl-3-methyl-butyl]-2,6-dimethyl-6,7-bis(oxidanyl)-1,4-oxazepane-3-carboxylic+acid'>A1I67</scene>, <scene name='pdbligand=A1JWF:(2~{S})-2-azanyl-3-tellurophen-2-yl-propanoic+acid'>A1JWF</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=HPE:HOMOPHENYLALANINE'>HPE</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9s78 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9s78 OCA], [https://pdbe.org/9s78 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9s78 RCSB], [https://www.ebi.ac.uk/pdbsum/9s78 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9s78 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/PSA2_YEAST 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. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Tracking small-molecule distribution in heterogeneous cell samples at single-cell resolution remains a major analytical challenge. Here, we present a tellurophene-functionalized analogue of the proteasome inhibitor Carfilzomib (TeCar) whose distribution can be followed by mass cytometric (MC) quantification while preserving target engagement and cytotoxicity. Structural and biochemical analyses confirm that TeCar binds the proteasome in a mode comparable to the clinically approved parent compound. Using MC, we demonstrate selective TeCar accumulation in malignant over immune cells within mixed populations, with cancer cells exhibiting 15 to 30-fold higher uptake. Tellurium signal correlates with proteasomal activity, and differential labeling among immune subsets reveals functional heterogeneity not captured by transcriptomics alone. These findings establish tellurophene tagging as a minimally perturbing and broadly applicable strategy for functional distribution studies at single-cell resolution. | ||
| - | + | Tellurophene-Tagged Carfilzomib Enables Single-Cell Mass Cytometric Mapping of Proteasome Activity.,Potter N, Eddenden A, Fomina A, Dinesh A, Jackson HW, McGuigan AP, Groll M, Nitz M ACS Chem Biol. 2025 Dec 19;20(12):2936-2942. doi: 10.1021/acschembio.5c00691. , Epub 2025 Nov 18. PMID:41252648<ref>PMID:41252648</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 9s78" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| - | [[Category: Eddenden | + | <references/> |
| - | [[Category: | + | __TOC__ |
| - | [[Category: Jackson | + | </StructureSection> |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: Nitz | + | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: | + | [[Category: Dinesh A]] |
| + | [[Category: Eddenden A]] | ||
| + | [[Category: Fomina A]] | ||
| + | [[Category: Groll M]] | ||
| + | [[Category: Jackson HW]] | ||
| + | [[Category: McGuigan A]] | ||
| + | [[Category: Nitz M]] | ||
| + | [[Category: Potter N]] | ||
Current revision
Yeast 20S Proteasome in Complex with Tellurophene-Tagged Carfilzomib
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