View source for 4qlt


==yCP in complex with tripeptidic epoxyketone inhibitor 2 (PR924)==
<StructureSection load='4qlt' size='340' side='right'caption='[[4qlt]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4qlt]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QLT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QLT 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]] 2.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=39V:N-[(3-METHYL-1H-INDEN-2-YL)CARBONYL]-D-ALANYL-N-[(2S,4R)-5-HYDROXY-4-METHYL-3-OXO-1-PHENYLPENTAN-2-YL]-L-TRYPTOPHANAMIDE'>39V</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=4qlt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qlt OCA], [https://pdbe.org/4qlt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qlt RCSB], [https://www.ebi.ac.uk/pdbsum/4qlt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qlt 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 ==
Mammalian genomes encode seven catalytic proteasome subunits, namely, beta1c, beta2c, beta5c (assembled into constitutive 20S proteasome core particles), beta1i, beta2i, beta5i (incorporated into immunoproteasomes), and the thymoproteasome-specific subunit beta5t. Extensive research in the past decades has yielded numerous potent proteasome inhibitors including compounds currently used in the clinic to treat multiple myeloma and mantle cell lymphoma. Proteasome inhibitors that selectively target combinations of beta1c/beta1i, beta2c/beta2i, or beta5c/beta5i are available, yet ligands truly selective for a single proteasome activity are scarce. In this work we report the development of cell-permeable beta1i and beta5i selective inhibitors that outperform existing leads in terms of selectivity and/or potency. These compounds are the result of a rational design strategy using known inhibitors as starting points and introducing structural features according to the X-ray structures of the murine constitutive and immunoproteasome 20S core particles.

Structure-Based Design of beta1i or beta5i Specific Inhibitors of Human Immunoproteasomes.,de Bruin G, Huber EM, Xin BT, van Rooden EJ, Al-Ayed K, Kim KB, Kisselev AF, Driessen C, van der Stelt M, van der Marel GA, Groll M, Overkleeft HS J Med Chem. 2014 Jul 15. PMID:25006746<ref>PMID:25006746</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4qlt" style="background-color:#fffaf0;"></div>

==See Also==
*[[Proteasome 3D structures|Proteasome 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae S288C]]
[[Category: Al-Ayed K]]
[[Category: Driessen C]]
[[Category: Groll M]]
[[Category: Huber E]]
[[Category: Kim K]]
[[Category: Kisselev A]]
[[Category: Overkleeft H]]
[[Category: Xin B]]
[[Category: De Bruin G]]
[[Category: Van Rooden E]]
[[Category: Van der Marel G]]