4r3o: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4r3o]] is a 20 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=4R3O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R3O FirstGlance]. <br>
<table><tr><td colspan='2'>[[4r3o]] is a 20 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=4R3O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R3O FirstGlance]. <br>
</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=4r3o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r3o OCA], [https://pdbe.org/4r3o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r3o RCSB], [https://www.ebi.ac.uk/pdbsum/4r3o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r3o ProSAT]</span></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</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=4r3o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r3o OCA], [https://pdbe.org/4r3o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r3o RCSB], [https://www.ebi.ac.uk/pdbsum/4r3o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r3o ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== 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.
[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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4r3o" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Proteasome 3D structures|Proteasome 3D structures]]
*[[Proteasome 3D structures|Proteasome 3D structures]]
== References ==
<references/>
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</StructureSection>
</StructureSection>

Latest revision as of 12:50, 1 March 2024

Human Constitutive 20S Proteasome

4r3o, resolution 2.60Å

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