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==CryoEM structure of human 20S proteasome in complex with proteasome inhibitor Salinosporamid A==
<StructureSection load='9hmn' size='340' side='right'caption='[[9hmn]], [[Resolution|resolution]] 2.55&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9hmn]] 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=9HMN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9HMN FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.55&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SA1:(3AR,6R,6AS)-6-((S)-((S)-CYCLOHEX-2-ENYL)(HYDROXY)METHYL)-6A-METHYL-4-OXO-HEXAHYDRO-2H-FURO[3,2-C]PYRROLE-6-CARBALDEHYDE'>SA1</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=9hmn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9hmn OCA], [https://pdbe.org/9hmn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9hmn RCSB], [https://www.ebi.ac.uk/pdbsum/9hmn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9hmn ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PSA2_HUMAN PSA2_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. PSMA2 may have a potential regulatory effect on another component(s) of the proteasome complex through tyrosine phosphorylation.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The 20S proteasome, a critical component of the ubiquitin-proteasome system, plays a central role in regulating protein degradation in eukaryotic cells. Marizomib (MZB), a natural gamma-lactam-beta-lactone compound derived from Salinispora tropica, is a potent 20S proteasome covalent inhibitor with demonstrated anticancer properties. Its broad-spectrum inhibition of all three proteasome subunits and ability to cross the blood-brain barrier has made it a promising therapeutic candidate for glioblastoma. Here, we present the cryo-EM structure of the human 20S proteasome in complex with MZB at 2.55 A resolution. This structure reveals the binding mode of MZB to all six catalytic subunits within the two beta-rings of the 20S proteasome, providing a detailed molecular understanding of its irreversible inhibitory mechanism. These findings explain the therapeutic potential of MZB at the molecular level and highlight marine-derived natural products in targeting the proteasome for anticancer treatment.

Structural insights into Salinosporamide A mediated inhibition of the human 20S proteasome.,Sulzen H, Fajtova P, O'Donoghue AJ, Boura E, Silhan J bioRxiv [Preprint]. 2025 Jan 28:2025.01.28.635221. doi: , 10.1101/2025.01.28.635221. PMID:39974992<ref>PMID:39974992</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9hmn" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Boura E]]
[[Category: Silhan J]]
[[Category: Suelzen H]]