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==Crystal structure of human Mms2/Ubc13 - NSC697923== | ==Crystal structure of human Mms2/Ubc13 - NSC697923== | ||
<StructureSection load='4onm' size='340' side='right' caption='[[4onm]], [[Resolution|resolution]] 1.35Å' scene=''> | <StructureSection load='4onm' size='340' side='right'caption='[[4onm]], [[Resolution|resolution]] 1.35Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4onm]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4onm]] 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=4ONM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ONM FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=N2F:2-[(4-METHYLPHENYL)SULFONYL]-5-NITROFURAN'>N2F</scene | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=N2F:2-[(4-METHYLPHENYL)SULFONYL]-5-NITROFURAN'>N2F</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=4onm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4onm OCA], [https://pdbe.org/4onm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4onm RCSB], [https://www.ebi.ac.uk/pdbsum/4onm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4onm ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/UB2V2_HUMAN UB2V2_HUMAN] Has no ubiquitin ligase activity on its own. The UBE2V2/UBE2N heterodimer catalyzes the synthesis of non-canonical poly-ubiquitin chains that are linked through 'Lys-63'. This type of poly-ubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage.<ref>PMID:9705497</ref> <ref>PMID:10089880</ref> <ref>PMID:14562038</ref> <ref>PMID:20061386</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 21: | Line 18: | ||
</div> | </div> | ||
<div class="pdbe-citations 4onm" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4onm" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Edwards | [[Category: Edwards RA]] | ||
[[Category: Glover | [[Category: Glover JNM]] | ||
[[Category: Hodge | [[Category: Hodge CD]] | ||
Revision as of 10:34, 25 January 2023
Crystal structure of human Mms2/Ubc13 - NSC697923Crystal structure of human Mms2/Ubc13 - NSC697923
Structural highlights
FunctionUB2V2_HUMAN Has no ubiquitin ligase activity on its own. The UBE2V2/UBE2N heterodimer catalyzes the synthesis of non-canonical poly-ubiquitin chains that are linked through 'Lys-63'. This type of poly-ubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage.[1] [2] [3] [4] Publication Abstract from PubMedUbc13 is an E2 ubiquitin conjugating enzyme that functions in nuclear DNA damage signaling and cytoplasmic NF-kappaB signaling. Here, we present the structures of complexes of Ubc13 with two inhibitors, NSC697923 and BAY 11-7082, which inhibit DNA damage and NF-kappaB signaling in human cells. NSC697923 and BAY 11-7082 both inhibit Ubc13 by covalent adduct formation through a Michael addition at the Ubc13 active site cysteine. The resulting adducts of both compounds exploit a binding groove unique to Ubc13. We developed a Ubc13 mutant which resists NSC697923 inhibition and, using this mutant, we show that the inhibition of cellular DNA damage and NF-kappaB signaling by NSC697923 is largely due to specific Ubc13 inhibition. We propose that unique structural features near the Ubc13 active site could provide a basis for the rational development and design of specific Ubc13 inhibitors. Covalent Inhibition of Ubc13 Affects Ubiquitin Signaling and Reveals Active Site Elements Important for Targeting.,Hodge CD, Edwards RA, Markin CJ, McDonald D, Pulvino M, Huen MS, Zhao J, Spyracopoulos L, Hendzel MJ, Glover JN ACS Chem Biol. 2015 May 1. PMID:25909880[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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