View source for 5mnj


==Structure of MDM2-MDMX-UbcH5B-ubiquitin complex==
<StructureSection load='5mnj' size='340' side='right'caption='[[5mnj]], [[Resolution|resolution]] 2.16&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5mnj]] is a 8 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=5MNJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MNJ 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]] 2.16&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5mnj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mnj OCA], [https://pdbe.org/5mnj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mnj RCSB], [https://www.ebi.ac.uk/pdbsum/5mnj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mnj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/UB2D2_HUMAN UB2D2_HUMAN] Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-linked polyubiquitination. Mediates the selective degradation of short-lived and abnormal proteins. Functions in the E6/E6-AP-induced ubiquitination of p53/TP53. Mediates ubiquitination of PEX5 and autoubiquitination of STUB1 and TRAF6. Involved in the signal-induced conjugation and subsequent degradation of NFKBIA, FBXW2-mediated GCM1 ubiquitination and degradation, MDM2-dependent degradation of p53/TP53 and the activation of MAVS in the mitochondria by DDX58/RIG-I in response to viral infection. Essential for viral activation of IRF3.<ref>PMID:10329681</ref> <ref>PMID:15280377</ref> <ref>PMID:18042044</ref> <ref>PMID:18703417</ref> <ref>PMID:18359941</ref> <ref>PMID:19854139</ref> <ref>PMID:20403326</ref> <ref>PMID:20061386</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
MDM2-MDMX complexes bind the p53 tumor-suppressor protein, inhibiting p53's transcriptional activity and targeting p53 for proteasomal degradation. Inhibitors that disrupt binding between p53 and MDM2 efficiently activate a p53 response, but their use in the treatment of cancers that retain wild-type p53 may be limited by on-target toxicities due to p53 activation in normal tissue. Guided by a novel crystal structure of the MDM2-MDMX-E2(UbcH5B)-ubiquitin complex, we designed MDM2 mutants that prevent E2-ubiquitin binding without altering the RING-domain structure. These mutants lack MDM2's E3 activity but retain the ability to limit p53's transcriptional activity and allow cell proliferation. Cells expressing these mutants respond more quickly to cellular stress than cells expressing wild-type MDM2, but basal p53 control is maintained. Targeting the MDM2 E3-ligase activity could therefore widen the therapeutic window of p53 activation in tumors.

Structural analysis of MDM2 RING separates degradation from regulation of p53 transcription activity.,Nomura K, Klejnot M, Kowalczyk D, Hock AK, Sibbet GJ, Vousden KH, Huang DT Nat Struct Mol Biol. 2017 Jul;24(7):578-587. doi: 10.1038/nsmb.3414. Epub 2017, May 29. PMID:28553961<ref>PMID:28553961</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5mnj" style="background-color:#fffaf0;"></div>

==See Also==
*[[MDM2 3D structures|MDM2 3D structures]]
*[[MDM4|MDM4]]
*[[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: Huang DT]]
[[Category: Klejnot M]]