2y6e: Difference between revisions

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[[Image:2y6e.png|left|200px]]


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==Structure of the D1D2 domain of USP4, the conserved catalytic domain==
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<StructureSection load='2y6e' size='340' side='right'caption='[[2y6e]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2y6e]] is a 6 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=2Y6E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Y6E 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]] 2.4&#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=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
{{STRUCTURE_2y6e|  PDB=2y6e  |  SCENE= }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2y6e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y6e OCA], [https://pdbe.org/2y6e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2y6e RCSB], [https://www.ebi.ac.uk/pdbsum/2y6e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2y6e ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/UBP4_HUMAN UBP4_HUMAN] Hydrolase that deubiquitinates target proteins such as the receptor ADORA2A, PDPK1 and TRIM21. Deubiquitination of ADORA2A increases the amount of functional receptor at the cell surface. Plays a role in the regulation of quality control in the ER.<ref>PMID:7784062</ref> <ref>PMID:16316627</ref> <ref>PMID:16472766</ref> <ref>PMID:16339847</ref>
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== Publication Abstract from PubMed ==
Ubiquitin-specific protease USP4 is emerging as an important regulator of cellular pathways, including the TGF-beta response, NF-kappaB signalling and splicing, with possible roles in cancer. Here we show that USP4 has its catalytic triad arranged in a productive conformation. Nevertheless, it requires its N-terminal DUSP-Ubl domain to achieve full catalytic turnover. Pre-steady-state kinetics measurements reveal that USP4 catalytic domain activity is strongly inhibited by slow dissociation of ubiquitin after substrate hydrolysis. The DUSP-Ubl domain is able to enhance ubiquitin dissociation, hence promoting efficient turnover. In a mechanism that requires all USP4 domains, binding of the DUSP-Ubl domain promotes a change of a switching loop near the active site. This 'allosteric regulation of product discharge' provides a novel way of regulating deubiquitinating enzymes that may have relevance for other enzyme classes.


===UBIQUITIN SPECIFIC PROTEASE 4 IS INHIBITED BY ITS UBIQUITIN-LIKE DOMAIN===
The DUSP-Ubl domain of USP4 enhances its catalytic efficiency by promoting ubiquitin exchange.,Clerici M, Luna-Vargas MP, Faesen AC, Sixma TK Nat Commun. 2014 Nov 18;5:5399. doi: 10.1038/ncomms6399. PMID:25404403<ref>PMID:25404403</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2y6e" style="background-color:#fffaf0;"></div>


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==See Also==
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*[[Thioesterase 3D structures|Thioesterase 3D structures]]
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== References ==
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<references/>
{{ABSTRACT_PUBMED_21415856}}
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</StructureSection>
==About this Structure==
[[2y6e]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y6E OCA].
 
==Reference==
<ref group="xtra">PMID:021415856</ref><references group="xtra"/>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Ubiquitin thiolesterase]]
[[Category: Large Structures]]
[[Category: Dijk, W J.Van.]]
[[Category: Faesen AC]]
[[Category: Faesen, A C.]]
[[Category: Fish A]]
[[Category: Fish, A.]]
[[Category: Luna-Vargas MPA]]
[[Category: Luna-Vargas, M P.A.]]
[[Category: Rape M]]
[[Category: Rape, M.]]
[[Category: Sixma TK]]
[[Category: Sixma, T K.]]
[[Category: Van Dijk WJ]]

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