4uf5
From Proteopedia
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| - | ''' | + | ==Crystal structure of UCH-L5 in complex with inhibitory fragment of INO80G== |
| + | <StructureSection load='4uf5' size='340' side='right' caption='[[4uf5]], [[Resolution|resolution]] 3.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4uf5]] is a 2 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UF5 FirstGlance]. <br> | ||
| + | </td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.19.12 3.4.19.12] </span></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4uf5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uf5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4uf5 RCSB], [http://www.ebi.ac.uk/pdbsum/4uf5 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://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> [[http://www.uniprot.org/uniprot/NFRKB_HUMAN NFRKB_HUMAN]] Binds to the DNA consensus sequence 5'-GGGGAATCTCC-3'.<ref>PMID:18922472</ref> Putative regulatory component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. Modulates the deubiquitinase activity of UCHL5 in the INO80 complex.<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. | ||
| - | + | 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> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | == References == | |
| - | + | <references/> | |
| - | [[Category: | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| - | + | [[Category: Ubiquitinyl hydrolase 1]] | |
| - | + | [[Category: Dijk, W J.Van]] | |
[[Category: Ekkebus, R]] | [[Category: Ekkebus, R]] | ||
| + | [[Category: Oualid, F El]] | ||
[[Category: Ovaa, H]] | [[Category: Ovaa, H]] | ||
| + | [[Category: Sahtoe, D D]] | ||
| + | [[Category: Sixma, T K]] | ||
| + | [[Category: Deubiquitinating enzyme]] | ||
| + | [[Category: Hydrolase]] | ||
Revision as of 11:23, 4 March 2015
Crystal structure of UCH-L5 in complex with inhibitory fragment of INO80G
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