6dxh

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m (Protected "6dxh" [edit=sysop:move=sysop])
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'''Unreleased structure'''
 
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The entry 6dxh is ON HOLD
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==Structure of USP5 zinc-finger ubiquitin binding domain co-crystallized with 4-(4-tert-butylphenyl)-4-oxobutanoate==
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<StructureSection load='6dxh' size='340' side='right'caption='[[6dxh]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[6dxh]] is a 1 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=6DXH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DXH FirstGlance]. <br>
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</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&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HH4:4-(4-tert-butylphenyl)-4-oxobutanoic+acid'>HH4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6dxh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dxh OCA], [https://pdbe.org/6dxh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dxh RCSB], [https://www.ebi.ac.uk/pdbsum/6dxh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dxh ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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USP5 disassembles unanchored polyubiquitin chains to recycle free monoubiquitin, and is one of the 12 ubiquitin specific proteases featuring a zinc finger ubiquitin-binding domain (ZnF-UBD). This distinct structural module has been associated with substrate positioning or allosteric modulation of catalytic activity, but its cellular function remains unclear. We screened a chemical library focused on the ZnF-UBD of USP5, crystallized hits in complex with the protein, and generated a preliminary structure-activity relationship, which enables the development of more potent and selective compounds. This work serves as a framework for the discovery of a chemical probe to delineate the function of USP5 ZnF-UBD in proteasomal degradation and other ubiquitin signaling pathways in health and disease.
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Authors: Harding, R.J., Mann, M.K., Ravichandran, M., Ferreira de Freitas, R., Franzoni, I., Bountra, C., Edwards, A.M., Arrowsmith, C.M., Schapira, M., Structural Genomics Consortium (SGC)
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Discovery of Small Molecule Antagonists of the USP5 Zinc Finger Ubiquitin-Binding Domain.,Mann MK, Franzoni I, de Freitas RF, Tempel W, Houliston S, Smith L, Vedadi M, Arrowsmith CH, Harding RJ, Schapira M J Med Chem. 2019 Nov 27;62(22):10144-10155. doi: 10.1021/acs.jmedchem.9b00988., Epub 2019 Nov 12. PMID:31663737<ref>PMID:31663737</ref>
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Description: Structure of USP5 zinc-finger ubiquitin binding domain co-crystallized with 4-(4-tert-butylphenyl)-4-oxobutanoate
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Franzoni, I]]
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<div class="pdbe-citations 6dxh" style="background-color:#fffaf0;"></div>
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[[Category: Mann, M.K]]
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[[Category: Ravichandran, M]]
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==See Also==
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[[Category: Arrowsmith, C.M]]
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*[[Thioesterase 3D structures|Thioesterase 3D structures]]
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[[Category: Schapira, M]]
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== References ==
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[[Category: Edwards, A.M]]
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<references/>
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[[Category: Ferreira De Freitas, R]]
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__TOC__
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[[Category: Structural Genomics Consortium (Sgc)]]
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</StructureSection>
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[[Category: Harding, R.J]]
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[[Category: Homo sapiens]]
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[[Category: Bountra, C]]
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[[Category: Large Structures]]
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[[Category: Arrowsmith CH]]
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[[Category: Bountra C]]
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[[Category: Edwards AM]]
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[[Category: Ferreira de Freitas R]]
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[[Category: Franzoni I]]
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[[Category: Harding RJ]]
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[[Category: Mann MK]]
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[[Category: Ravichandran M]]
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[[Category: Schapira M]]

Current revision

Structure of USP5 zinc-finger ubiquitin binding domain co-crystallized with 4-(4-tert-butylphenyl)-4-oxobutanoate

PDB ID 6dxh

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