View source for 6qh3


==Catalytic domain of the human ubiquitin-conjugating enzyme UBE2S C118M==
<StructureSection load='6qh3' size='340' side='right'caption='[[6qh3]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6qh3]] 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=6QH3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QH3 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]] 2.9&#8491;</td></tr>
<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></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=6qh3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qh3 OCA], [https://pdbe.org/6qh3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qh3 RCSB], [https://www.ebi.ac.uk/pdbsum/6qh3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qh3 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/UBE2S_HUMAN UBE2S_HUMAN] Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. Catalyzes 'Lys-11'-linked polyubiquitination. Acts as an essential factor of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated ubiquitin ligase that controls progression through mitosis. Acts by specifically elongating 'Lys-11'-linked polyubiquitin chains initiated by the E2 enzyme UBE2C/UBCH10 on APC/C substrates, enhancing the degradation of APC/C substrates by the proteasome and promoting mitotic exit. Also acts by elongating ubiquitin chains initiated by the E2 enzyme UBE2D1/UBCH5 in vitro; it is however unclear whether UBE2D1/UBCH5 acts as a E2 enzyme for the APC/C in vivo. Also involved in ubiquitination and subsequent degradation of VHL, resulting in an accumulation of HIF1A. In vitro able to promote polyubiquitination using all 7 ubiquitin Lys residues, except 'Lys-48'-linked polyubiquitination.<ref>PMID:16819549</ref> <ref>PMID:19820702</ref> <ref>PMID:19822757</ref> <ref>PMID:20061386</ref> <ref>PMID:20622874</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Ubiquitin-conjugating enzymes (E2s) govern key aspects of ubiquitin signaling. Emerging evidence suggests that the activities of E2s are modulated by posttranslational modifications; the structural underpinnings, however, are largely unclear. Here, we unravel the structural basis and mechanistic consequences of a conserved autoubiquitination event near the catalytic center of E2s, using the human anaphase-promoting complex/cyclosome-associated UBE2S as a model system. Crystal structures we determined of the catalytic ubiquitin carrier protein domain combined with MD simulations reveal that the active-site region is malleable, which permits an adjacent ubiquitin acceptor site, Lys(+5), to be ubiquitinated intramolecularly. We demonstrate by NMR that the Lys(+5)-linked ubiquitin inhibits UBE2S by obstructing its reloading with ubiquitin. By immunoprecipitation, quantitative mass spectrometry, and siRNA-and-rescue experiments we show that Lys(+5) ubiquitination of UBE2S decreases during mitotic exit but does not influence proteasomal turnover of this E2. These findings suggest that UBE2S activity underlies inherent regulation during the cell cycle.

Autoinhibition Mechanism of the Ubiquitin-Conjugating Enzyme UBE2S by Autoubiquitination.,Liess AKL, Kucerova A, Schweimer K, Yu L, Roumeliotis TI, Diebold M, Dybkov O, Sotriffer C, Urlaub H, Choudhary JS, Mansfeld J, Lorenz S Structure. 2019 Jun 4. pii: S0969-2126(19)30170-4. doi:, 10.1016/j.str.2019.05.008. PMID:31230944<ref>PMID:31230944</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6qh3" style="background-color:#fffaf0;"></div>

==See Also==
*[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Liess AKL]]
[[Category: Lorenz S]]