4r67
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Human constitutive 20S proteasome in complex with carfilzomib== | |
| + | <StructureSection load='4r67' size='340' side='right'caption='[[4r67]], [[Resolution|resolution]] 2.89Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4r67]] is a 40 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R67 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R67 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]] 2.89Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3BV:N-{(2S)-2-[(MORPHOLIN-4-YLACETYL)AMINO]-4-PHENYLBUTANOYL}-L-LEUCYL-N-[(2R,3S,4S)-1,3-DIHYDROXY-2,6-DIMETHYLHEPTAN-4-YL]-L-PHENYLALANINAMIDE'>3BV</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=4r67 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r67 OCA], [https://pdbe.org/4r67 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r67 RCSB], [https://www.ebi.ac.uk/pdbsum/4r67 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r67 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/PSA6_HUMAN PSA6_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. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Proteasome inhibition is highly effective as a treatment for multiple myeloma, and recently carfilzomib was granted US FDA approval for the treatment of relapsed and refractory multiple myeloma. Here, we report the X-ray crystal structure of the human constitutive 20S proteasome with and without carfilzomib bound at 2.9 and 2.6 A, respectively. Our data indicate that the S3 and S4 binding pockets play a pivotal role in carfilzomib's selectivity for chymotrypsin-like sites. Structural comparison with the mouse immunoproteasome crystal structure reveals amino acid substitutions that explain carfilzomib's slight preference for chymotrypsin-like subunits of constitutive proteasomes. In addition, comparison of the human proteasome:carfilzomib complex with the mouse proteasome:PR-957 complex reveals new details that explain why PR-957 is selective for immunoproteasomes. Together, the data presented here support the design of inhibitors for either constitutive or immunoproteasomes, with implications for the treatment of cancers as well as autoimmune and neurodegenerative diseases. | ||
| - | + | Crystal Structure of the Human 20S Proteasome in Complex with Carfilzomib.,Harshbarger W, Miller C, Diedrich C, Sacchettini J Structure. 2015 Feb 3;23(2):418-24. doi: 10.1016/j.str.2014.11.017. Epub 2015 Jan, 15. PMID:25599644<ref>PMID:25599644</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Harshbarger | + | <div class="pdbe-citations 4r67" style="background-color:#fffaf0;"></div> |
| - | [[Category: Sacchettini | + | |
| + | ==See Also== | ||
| + | *[[Proteasome 3D structures|Proteasome 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Harshbarger WH]] | ||
| + | [[Category: Sacchettini JC]] | ||
Current revision
Human constitutive 20S proteasome in complex with carfilzomib
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