View source for 7myf


==Ubiquitin variant UbV.k.1 in complex with Ube2k==
<StructureSection load='7myf' size='340' side='right'caption='[[7myf]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7myf]] is a 3 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=7MYF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MYF 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&#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=7myf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7myf OCA], [https://pdbe.org/7myf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7myf RCSB], [https://www.ebi.ac.uk/pdbsum/7myf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7myf ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/UBE2K_HUMAN UBE2K_HUMAN] Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro, in the presence or in the absence of BRCA1-BARD1 E3 ubiquitin-protein ligase complex, catalyzes the synthesis of 'Lys-48'-linked polyubiquitin chains. Does not transfer ubiquitin directly to but elongates monoubiquitinated substrate protein. Mediates the selective degradation of short-lived and abnormal proteins, such as the endoplasmic reticulum-associated degradation (ERAD) of misfolded lumenal proteins. Ubiquitinates huntingtin. May mediate foam cell formation by the suppression of apoptosis of lipid-bearing macrophages through ubiquitination and subsequence degradation of p53/TP53. Proposed to be involved in ubiquitination and proteolytic processing of NF-kappa-B; in vitro supports ubiquitination of NFKB1. In case of infection by cytomegaloviruses may be involved in the US11-dependent degradation of MHC class I heavy chains following their export from the ER to the cytosol. In case of viral infections may be involved in the HPV E7 protein-dependent degradation of RB1.<ref>PMID:8702625</ref> <ref>PMID:10634809</ref> <ref>PMID:10675012</ref> <ref>PMID:16714285</ref> <ref>PMID:16868077</ref> <ref>PMID:17873885</ref> <ref>PMID:20061386</ref> <ref>PMID:19906396</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Transfer of ubiquitin to substrate proteins regulates most processes in eukaryotic cells. E2 enzymes are a central component of the ubiquitin machinery, and generally determine the type of ubiquitin signal generated and thus the ultimate fate of substrate proteins. The E2, Ube2k, specifically builds degradative ubiquitin chains on diverse substrates. Here we have identified protein-based reagents, called ubiquitin variants (UbVs), that bind tightly and specifically to Ube2k. Crystal structures reveal that the UbVs bind to the E2 enzyme at a hydrophobic cleft that is distinct from the active site and previously identified ubiquitin binding sites. We demonstrate that the UbVs are potent inhibitors of Ube2k and block both ubiquitin charging of the E2 enzyme and E3-catalyzed ubiquitin transfer. The binding site of the UbVs suggests they directly clash with the ubiquitin activating enzyme, while potentially disrupting interactions with E3 ligases via allosteric effects. Our data reveal the first protein-based inhibitors of Ube2k and unveil a hydrophobic groove that could be an effective target for inhibiting Ube2k and other E2 enzymes.

Identification of Ubiquitin Variants That Inhibit the E2 Ubiquitin Conjugating Enzyme, Ube2k.,Middleton AJ, Teyra J, Zhu J, Sidhu SS, Day CL ACS Chem Biol. 2021 Sep 17;16(9):1745-1756. doi: 10.1021/acschembio.1c00445. Epub , 2021 Aug 16. PMID:34397214<ref>PMID:34397214</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7myf" style="background-color:#fffaf0;"></div>

==See Also==
*[[3D structures of ubiquitin|3D structures of ubiquitin]]
*[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Day CL]]
[[Category: Middleton AJ]]
[[Category: Sidhu SS]]
[[Category: Teyra J]]