7ms6

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(New page: '''Unreleased structure''' The entry 7ms6 is ON HOLD Authors: Mann, M.K., Zepeda-Velazquez, C.A., Alvarez, H.G., Dong, A., Kiyota, T., Aman, A., Arrowsmith, C.H., Al-Awar, R., Harding, ...)
Current revision (16:19, 18 October 2023) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 7ms6 is ON HOLD
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==Structure of USP5 zinc-finger ubiquitin binding domain co-crystallized with (2-fluoro-4-((4-phenylpiperidin-1-yl)sulfonyl)benzoyl)glycine==
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<StructureSection load='7ms6' size='340' side='right'caption='[[7ms6]], [[Resolution|resolution]] 1.55&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[7ms6]] 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=7MS6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MS6 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]] 1.55&#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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=ZPV:N-[2-fluoro-4-(4-phenylpiperidine-1-sulfonyl)benzoyl]glycine'>ZPV</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=7ms6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ms6 OCA], [https://pdbe.org/7ms6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ms6 RCSB], [https://www.ebi.ac.uk/pdbsum/7ms6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ms6 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 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.
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Authors: Mann, M.K., Zepeda-Velazquez, C.A., Alvarez, H.G., Dong, A., Kiyota, T., Aman, A., Arrowsmith, C.H., Al-Awar, R., Harding, R.J., Schapira, M.
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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>
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Description: Structure of USP5 zinc-finger ubiquitin binding domain co-crystallized with (2-fluoro-4-((4-phenylpiperidin-1-yl)sulfonyl)benzoyl)glycine
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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: Schapira, M]]
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<div class="pdbe-citations 7ms6" style="background-color:#fffaf0;"></div>
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[[Category: Zepeda-Velazquez, C.A]]
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[[Category: Arrowsmith, C.H]]
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==See Also==
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[[Category: Mann, M.K]]
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*[[Thioesterase 3D structures|Thioesterase 3D structures]]
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[[Category: Dong, A]]
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== References ==
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[[Category: Harding, R.J]]
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<references/>
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[[Category: Aman, A]]
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__TOC__
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[[Category: Kiyota, T]]
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</StructureSection>
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[[Category: Alvarez, H.G]]
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[[Category: Homo sapiens]]
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[[Category: Al-Awar, R]]
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[[Category: Large Structures]]
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[[Category: Al-Awar R]]
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[[Category: Alvarez HG]]
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[[Category: Aman A]]
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[[Category: Arrowsmith CH]]
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[[Category: Dong A]]
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[[Category: Harding RJ]]
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[[Category: Kiyota T]]
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[[Category: Mann MK]]
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[[Category: Schapira M]]
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[[Category: Zepeda-Velazquez CA]]

Current revision

Structure of USP5 zinc-finger ubiquitin binding domain co-crystallized with (2-fluoro-4-((4-phenylpiperidin-1-yl)sulfonyl)benzoyl)glycine

PDB ID 7ms6

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