4uf5: Difference between revisions

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'''Unreleased structure'''


The entry 4uf5 is ON HOLD
==Crystal structure of UCH-L5 in complex with inhibitory fragment of INO80G==
<StructureSection load='4uf5' size='340' side='right'caption='[[4uf5]], [[Resolution|resolution]] 3.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4uf5]] 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=4UF5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UF5 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.7&#8491;</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=4uf5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uf5 OCA], [https://pdbe.org/4uf5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4uf5 RCSB], [https://www.ebi.ac.uk/pdbsum/4uf5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4uf5 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/UCHL5_HUMAN UCHL5_HUMAN] Protease that specifically cleaves 'Lys-48'-linked polyubiquitin chains. Deubiquitinating enzyme associated with the 19S regulatory subunit of the 26S proteasome. Putative regulatory component of the INO80 complex; however is inactive in the INO80 complex and is activated by a transient interaction of the INO80 complex with the proteasome via ADRM1.<ref>PMID:16906146</ref> <ref>PMID:18922472</ref>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Deubiquitinating enzymes (DUBs) control vital processes in eukaryotes by hydrolyzing ubiquitin adducts. Their activities are tightly regulated, but the mechanisms remain elusive. In particular, the DUB UCH-L5 can be either activated or inhibited by conserved regulatory proteins RPN13 and INO80G, respectively. Here we show how the DEUBAD domain in RPN13 activates UCH-L5 by positioning its C-terminal ULD domain and crossover loop to promote substrate binding and catalysis. The related DEUBAD domain in INO80G inhibits UCH-L5 by exploiting similar structural elements in UCH-L5 to promote a radically different conformation, and employs molecular mimicry to block ubiquitin docking. In this process, large conformational changes create small but highly specific interfaces that mediate activity modulation of UCH-L5 by altering the affinity for substrates. Our results establish how related domains can exploit enzyme conformational plasticity to allosterically regulate DUB activity. These allosteric sites may present novel insights for pharmaceutical intervention in DUB activity.


Authors: Sahtoe, D.D., Van Dijk, W.J., El Oualid, F., Ekkebus, R., Ovaa, H., Sixma, T.K.
Mechanism of UCH-L5 Activation and Inhibition by DEUBAD Domains in RPN13 and INO80G.,Sahtoe DD, van Dijk WJ, El Oualid F, Ekkebus R, Ovaa H, Sixma TK Mol Cell. 2015 Feb 17. pii: S1097-2765(14)01017-X. doi:, 10.1016/j.molcel.2014.12.039. PMID:25702870<ref>PMID:25702870</ref>


Description: Crystal structure of UCH-L5 in complex with inhibitory fragment of INO80G
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: El Oualid, F]]
<div class="pdbe-citations 4uf5" style="background-color:#fffaf0;"></div>
[[Category: Van Dijk, W.J]]
 
[[Category: Sahtoe, D.D]]
==See Also==
[[Category: Sixma, T.K]]
*[[Thioesterase 3D structures|Thioesterase 3D structures]]
[[Category: Ekkebus, R]]
== References ==
[[Category: Ovaa, H]]
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ekkebus R]]
[[Category: El Oualid F]]
[[Category: Ovaa H]]
[[Category: Sahtoe DD]]
[[Category: Sixma TK]]
[[Category: Van Dijk WJ]]

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