View source for 6d68


==Ube2G1 in complex with ubiquitin variant Ubv.G1.1==
<StructureSection load='6d68' size='340' side='right'caption='[[6d68]], [[Resolution|resolution]] 2.36&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6d68]] is a 4 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=6D68 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6D68 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]] 2.36&#8491;</td></tr>
<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></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=6d68 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d68 OCA], [https://pdbe.org/6d68 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6d68 RCSB], [https://www.ebi.ac.uk/pdbsum/6d68 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6d68 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/UB2G1_HUMAN UB2G1_HUMAN] Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-, as well as 'Lys-63'-linked polyubiquitination. May be involved in degradation of muscle-specific proteins. Mediates polyubiquitination of CYP3A4.<ref>PMID:19103148</ref> <ref>PMID:20061386</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Ubiquitin-conjugating E2 enzymes are central to the ubiquitination cascade and have been implicated in cancer and other diseases. Despite strong interest in developing specific E2 inhibitors, the shallow and exposed active site has proven recalcitrant to targeting with reversible small-molecule inhibitors. Here, we used phage display to generate highly potent and selective ubiquitin variants (UbVs) that target the E2 backside, which is located opposite to the active site. A UbV targeting Ube2D1 did not affect charging but greatly attenuated chain elongation. Likewise, a UbV targeting the E2 variant Ube2V1 did not interfere with the charging of its partner E2 enzyme but inhibited formation of di-ubiquitin. In contrast, a UbV that bound to the backside of Ube2G1 impeded the generation of thioester-linked ubiquitin to the active site cysteine of Ube2G1 by the E1 enzyme. Crystal structures of UbVs in complex with three E2 proteins revealed distinctive molecular interactions in each case, but they also highlighted a common backside pocket that the UbVs utilized for enhanced affinity and specificity. These findings validate the E2 backside as a target for inhibition and provide structural insights to aid inhibitor design and screening efforts.

Structural and Functional Analysis of Ubiquitin-based inhibitors that Target the Backsides of E2 Enzymes.,Garg P, Ceccarelli DF, Keszei AF, Kourinov I, Sicheri F, Sidhu SS J Mol Biol. 2019 Oct 18. pii: S0022-2836(18)30280-8. doi:, 10.1016/j.jmb.2019.09.024. PMID:31634471<ref>PMID:31634471</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6d68" style="background-color:#fffaf0;"></div>

==See Also==
*[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ceccarelli DF]]
[[Category: Garg P]]
[[Category: Sicheri F]]
[[Category: Sidhu S]]