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<StructureSection load='6v4h' size='340' side='right'caption='[[6v4h]], [[Resolution|resolution]] 1.53&Aring;' scene=''>
<StructureSection load='6v4h' size='340' side='right'caption='[[6v4h]], [[Resolution|resolution]] 1.53&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6v4h]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V4H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V4H FirstGlance]. <br>
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V4H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V4H 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]] 1.53&#8491;</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.53&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0EH:(2R)-2-AMINO-2-METHYLNONANOIC+ACID'>0EH</scene>, <scene name='pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0EH:(2R)-2-AMINO-2-METHYLNONANOIC+ACID'>0EH</scene>, <scene name='pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=6v4h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v4h OCA], [https://pdbe.org/6v4h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v4h RCSB], [https://www.ebi.ac.uk/pdbsum/6v4h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v4h ProSAT]</span></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=6v4h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v4h OCA], [https://pdbe.org/6v4h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v4h RCSB], [https://www.ebi.ac.uk/pdbsum/6v4h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v4h ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MDM4_DANRE MDM4_DANRE] Inhibits p53- and p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
p53 is a critical tumor-suppressor protein that guards the human genome against mutations by inducing cell-cycle arrest or apoptosis. Cancer cells subvert p53 by deletion, mutation, or overexpression of the negative regulators HDM2 and HDMX. For tumors that retain wild-type p53, its reactivation by pharmacologic targeting of HDM2 and/or HDMX represents a promising strategy, with a series of selective small-molecule HDM2 inhibitors and a dual HDM2/HDMX stapled-peptide inhibitor being evaluated in clinical trials. Because selective HDM2 targeting can cause hematologic toxicity, selective HDMX inhibitors could provide an alternative p53-reactivation strategy, but clinical candidates remain elusive. Here, we applied a mutation-scanning approach to uncover p53-based stapled peptides that are selective for HDMX. Crystal structures of stapled-peptide/HDMX complexes revealed a molecular mechanism for the observed specificity, which was validated by HDMX mutagenesis. Thus, we provide a blueprint for the development of HDMX-selective inhibitors to dissect and target the p53/HDMX interaction.
Identification of a Structural Determinant for Selective Targeting of HDMX.,Ben-Nun Y, Seo HS, Harvey EP, Hauseman ZJ, Wales TE, Newman CE, Cathcart AM, Engen JR, Dhe-Paganon S, Walensky LD Structure. 2020 Jul 7;28(7):847-857.e5. doi: 10.1016/j.str.2020.04.011. Epub 2020, Apr 30. PMID:32359398<ref>PMID:32359398</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6v4h" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[MDM4|MDM4]]
*[[MDM4|MDM4]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Danio rerio]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Dhe-Paganon S]]
[[Category: Dhe-Paganon S]]
[[Category: Seo H-S]]
[[Category: Seo H-S]]

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