3mg0: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:3mg0.jpg|left|200px]]
-<!--
+==Structure of yeast 20S proteasome with bortezomib==
-The line below this paragraph, containing "STRUCTURE_3mg0", creates the "Structure Box" on the page.
+<StructureSection load='3mg0' size='340' side='right'caption='[[3mg0]], [[Resolution|resolution]] 2.68&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3mg0]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MG0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MG0 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.68&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BO2:N-[(1R)-1-(DIHYDROXYBORYL)-3-METHYLBUTYL]-N-(PYRAZIN-2-YLCARBONYL)-L-PHENYLALANINAMIDE'>BO2</scene></td></tr>
-{{STRUCTURE_3mg0|  PDB=3mg0  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3mg0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mg0 OCA], [https://pdbe.org/3mg0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mg0 RCSB], [https://www.ebi.ac.uk/pdbsum/3mg0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mg0 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 ==
+The mammalian 26S proteasome is a 2500 kDa multi-catalytic complex involved in intracellular protein degradation. We describe the synthesis and properties of a novel series of non-covalent di-peptide inhibitors of the proteasome based [corrected] on a capped tri-peptide that was first identified by high-throughput screening of a library of approx. 350000 compounds for inhibitors of the ubiquitin-proteasome system in cells. We show that these compounds are entirely selective for the beta5 (chymotrypsin-like) site over the beta1 (caspase-like) and beta2 (trypsin-like) sites of the 20S core particle of the proteasome, and over a panel of less closely related proteases. Compound optimization, guided by X-ray crystallography of the liganded 20S core particle, confirmed their non-covalent binding mode and provided a structural basis for their enhanced in vitro and cellular potencies. We demonstrate that such compounds show low nanomolar IC50 values for the human 20S beta5 site in vitro, and that pharmacological inhibition of this site in cells is sufficient to potently inhibit the degradation of a tetra-ubiquitin-luciferase reporter, activation of NFkappaB (nuclear factor kappaB) in response to TNF-alpha (tumour necrosis factor-alpha) and the proliferation of cancer cells. Finally, we identified capped di-peptides that show differential selectivity for the beta5 site of the constitutively expressed proteasome and immunoproteasome in vitro and in B-cell lymphomas. Collectively, these studies describe the synthesis, activity and binding mode of a new series of non-covalent proteasome inhibitors with unprecedented potency and selectivity for the beta5 site, and which can discriminate between the constitutive proteasome and immunoproteasome in vitro and in cells.
-===Structure of yeast 20S proteasome with bortezomib===
+Characterization of a new series of non-covalent proteasome inhibitors with exquisite potency and selectivity for the 20S beta5-subunit.,Blackburn C, Gigstad KM, Hales P, Garcia K, Jones M, Bruzzese FJ, Barrett C, Liu JX, Soucy TA, Sappal DS, Bump N, Olhava EJ, Fleming P, Dick LR, Tsu C, Sintchak MD, Blank JL Biochem J. 2010 Aug 27;430(3):461-76. PMID:20632995<ref>PMID:20632995</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3mg0" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_20632995}}, adds the Publication Abstract to the page
+*[[Proteasome 3D structures|Proteasome 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 20632995 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_20632995}}
+__TOC__
+</StructureSection>
-==About this Structure==
+[[Category: Large Structures]]
-[[3mg0]] is a 28 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MG0 OCA].
-==Reference==
-<ref group="xtra">PMID:020632995</ref><references group="xtra"/>
-[[Category: Proteasome endopeptidase complex]]
 [[Category: Saccharomyces cerevisiae]]
-[[Category: Sintchak, M D.]]
+[[Category: Sintchak MD]]