7ms7: Difference between revisions
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<StructureSection load='7ms7' size='340' side='right'caption='[[7ms7]], [[Resolution|resolution]] 1.45Å' scene=''> | <StructureSection load='7ms7' size='340' side='right'caption='[[7ms7]], [[Resolution|resolution]] 1.45Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7ms7]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[7ms7]] is a 2 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=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='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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.45Å</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='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> | <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> | </table> | ||
== Function == | == 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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 7ms7" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 7ms7" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Thioesterase 3D structures|Thioesterase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Al-Awar R]] | |||
[[Category: Al-Awar | [[Category: Alvarez HG]] | ||
[[Category: Alvarez | [[Category: Aman A]] | ||
[[Category: Aman | [[Category: Arrowsmith CH]] | ||
[[Category: Arrowsmith | [[Category: Dong A]] | ||
[[Category: Dong | [[Category: Harding RJ]] | ||
[[Category: Harding | [[Category: Kiyota T]] | ||
[[Category: Kiyota | [[Category: Mann MK]] | ||
[[Category: Mann | [[Category: Schapira M]] | ||
[[Category: Schapira | [[Category: Zepeda-Velazquez CA]] | ||
[[Category: Zepeda-Velazquez | |||
Revision as of 19:19, 18 October 2023
Structure of USP5 zinc-finger ubiquitin binding domain co-crystallized with (5-((4-(4-chlorophenyl)piperidin-1-yl)sulfonyl)picolinoyl)glycineStructure of USP5 zinc-finger ubiquitin binding domain co-crystallized with (5-((4-(4-chlorophenyl)piperidin-1-yl)sulfonyl)picolinoyl)glycine
Structural highlights
FunctionUBP5_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.[1] Publication Abstract from PubMedUSP5 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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