7ms7: Difference between revisions

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 ==Structure of USP5 zinc-finger ubiquitin binding domain co-crystallized with (5-((4-(4-chlorophenyl)piperidin-1-yl)sulfonyl)picolinoyl)glycine==
-<StructureSection load='7ms7' size='340' side='right'caption='[[7ms7]]' scene=''>
+<StructureSection load='7ms7' size='340' side='right'caption='[[7ms7]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MS7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MS7 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7ms7]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MS7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MS7 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=7ms7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ms7 OCA], [https://pdbe.org/7ms7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ms7 RCSB], [https://www.ebi.ac.uk/pdbsum/7ms7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ms7 ProSAT]</span></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=ZQ1:N-{5-[4-(4-chlorophenyl)piperidine-1-sulfonyl]pyridine-2-carbonyl}glycine'>ZQ1</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">USP5, ISOT ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase 1], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.19.12 3.4.19.12] </span></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=7ms7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ms7 OCA], [https://pdbe.org/7ms7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ms7 RCSB], [https://www.ebi.ac.uk/pdbsum/7ms7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ms7 ProSAT]</span></td></tr>
 </table>
+== Function ==
+[[https://www.uniprot.org/uniprot/UBP5_HUMAN UBP5_HUMAN]] Cleaves linear and branched multiubiquitin polymers with a marked preference for branched polymers. Involved in unanchored 'Lys-48'-linked polyubiquitin disassembly. Binds linear and 'Lys-63'-linked polyubiquitin with a lower affinity. Knock-down of USP5 causes the accumulation of p53/TP53 and an increase in p53/TP53 transcriptional activity because the unanchored polyubiquitin that accumulates is able to compete with ubiquitinated p53/TP53 but not with MDM2 for proteasomal recognition.<ref>PMID:19098288</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+USP5 is a deubiquitinase that has been implicated in a range of diseases, including cancer, but no USP5-targeting chemical probe has been reported to date. Here, we present the progression of a chemical series that occupies the C-terminal ubiquitin-binding site of a poorly characterized zinc-finger ubiquitin binding domain (ZnF-UBD) of USP5 and competitively inhibits the catalytic activity of the enzyme. Exploration of the structure-activity relationship, complemented with crystallographic characterization of the ZnF-UBD bound to multiple ligands, led to the identification of 64, which binds to the USP5 ZnF-UBD with a KD of 2.8 muM and is selective over nine proteins containing structurally similar ZnF-UBD domains. 64 inhibits the USP5 catalytic cleavage of a di-ubiquitin substrate in an in vitro assay. This study provides a chemical and structural framework for the discovery of a chemical probe to delineate USP5 function in cells.
+Structure-Activity Relationship of USP5 Inhibitors.,Mann MK, Zepeda-Velazquez CA, Gonzalez-Alvarez H, Dong A, Kiyota T, Aman AM, Loppnau P, Li Y, Wilson B, Arrowsmith CH, Al-Awar R, Harding RJ, Schapira M J Med Chem. 2021 Oct 14. doi: 10.1021/acs.jmedchem.1c00889. PMID:34648286<ref>PMID:34648286</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 7ms7" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: Al-Awar R]]
+[[Category: Ubiquitinyl hydrolase 1]]
-[[Category: Alvarez HG]]
+[[Category: Al-Awar, R]]
-[[Category: Aman A]]
+[[Category: Alvarez, H G]]
-[[Category: Arrowsmith CH]]
+[[Category: Aman, A]]
-[[Category: Dong A]]
+[[Category: Arrowsmith, C H]]
-[[Category: Harding RJ]]
+[[Category: Dong, A]]
-[[Category: Kiyota T]]
+[[Category: Harding, R J]]
-[[Category: Mann MK]]
+[[Category: Kiyota, T]]
-[[Category: Schapira M]]
+[[Category: Mann, M K]]
-[[Category: Zepeda-Velazquez CA]]
+[[Category: Schapira, M]]
+[[Category: Zepeda-Velazquez, C A]]
+[[Category: Hydrolase]]
+[[Category: Hydrolase-inhibitor complex]]
+[[Category: Ubiquitin]]
+[[Category: Ubiquitin specific protease]]
+[[Category: Usp]]
+[[Category: Usp5]]