View source for 8bzl


==Human 20S Proteasome in complex with peptide activator peptide BLM42==
<StructureSection load='8bzl' size='340' side='right'caption='[[8bzl]], [[Resolution|resolution]] 2.14&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8bzl]] 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=8BZL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BZL 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]] 2.14&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NEN:1-ETHYL-PYRROLIDINE-2,5-DIONE'>NEN</scene>, <scene name='pdbligand=YCM:S-(2-AMINO-2-OXOETHYL)-L-CYSTEINE'>YCM</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=8bzl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bzl OCA], [https://pdbe.org/8bzl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bzl RCSB], [https://www.ebi.ac.uk/pdbsum/8bzl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bzl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PSB3_HUMAN PSB3_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.
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== Publication Abstract from PubMed ==
Proteasomes catalyze protein degradation in cells and play an integral role in cellular homeostasis. Its activity decreases with age alongside the load of defective proteins, resulting from mutations or oxidative stress-induced damage. Such proteins are prone to aggregation and, if not efficiently degraded, can form toxic oligomers and amyloid plaques. Developing an effective way to activate the proteasome could prevent such pathologies. Designing activators is not easy because they do not bind in the active site, which is well-defined and highly conserved, but away from it. The structures of proteasome complexes with natural activators can help here, but these are large proteins, some even multimeric, whose activity is difficult to replace with a small-molecule compound. Nevertheless, the use of fragments of such proteins makes it possible to accumulate knowledge about the relevance of various structural elements for efficient and selective activation. Here, we presented peptidic activators of the 20S proteasome, which were designed based on both the C-terminal sequence of the yeast proteasome activator, Blm10 protein, and the interactions predicted by molecular modeling. These Blm analogs were able to stimulate human 20S proteasome to more efficiently degrade both small fluorogenic substrates and proteins. The best activators also demonstrated their efficacy in cell lysates. X-ray crystallography indicated that an effective modulator can bind to several sites on the surface of the proteasome without causing permanent structural changes in its immediate vicinity but affecting the active sites.

Blm10-Based Compounds Add to the Knowledge of How Allosteric Modulators Influence Human 20S Proteasome.,Witkowska J, Gizynska M, Karpowicz P, Sowik D, Trepczyk K, Hennenberg F, Chari A, Gieldon A, Pierzynowska K, Gaffke L, Wegrzyn G, Jankowska E ACS Chem Biol. 2025 Feb 21;20(2):266-280. doi: 10.1021/acschembio.4c00341. Epub , 2025 Feb 5. PMID:39907714<ref>PMID:39907714</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8bzl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chari A]]
[[Category: Henneberg F]]
[[Category: Jankowska E]]
[[Category: Witkowska J]]