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==The 1.9A crystal structure of humanized Xenopus Mdm2 with nutlin-3a==
==The 1.9A crystal structure of humanized Xenopus Mdm2 with nutlin-3a==
<StructureSection load='4j3e' size='340' side='right' caption='[[4j3e]], [[Resolution|resolution]] 1.91&Aring;' scene=''>
<StructureSection load='4j3e' size='340' side='right'caption='[[4j3e]], [[Resolution|resolution]] 1.91&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4j3e]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/African_clawed_frog African clawed frog]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J3E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4J3E FirstGlance]. <br>
<table><tr><td colspan='2'>[[4j3e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J3E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4J3E FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NUT:4-({(4S,5R)-4,5-BIS(4-CHLOROPHENYL)-2-[4-METHOXY-2-(PROPAN-2-YLOXY)PHENYL]-4,5-DIHYDRO-1H-IMIDAZOL-1-YL}CARBONYL)PIPERAZIN-2-ONE'>NUT</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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]] 1.91&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ipf|4ipf]], [[1rv1|1rv1]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NUT:4-({(4S,5R)-4,5-BIS(4-CHLOROPHENYL)-2-[4-METHOXY-2-(PROPAN-2-YLOXY)PHENYL]-4,5-DIHYDRO-1H-IMIDAZOL-1-YL}CARBONYL)PIPERAZIN-2-ONE'>NUT</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mdm2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=8355 African clawed frog])</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=4j3e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j3e OCA], [https://pdbe.org/4j3e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4j3e RCSB], [https://www.ebi.ac.uk/pdbsum/4j3e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4j3e ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4j3e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j3e OCA], [http://pdbe.org/4j3e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4j3e RCSB], [http://www.ebi.ac.uk/pdbsum/4j3e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4j3e ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/MDM2_XENLA MDM2_XENLA]] E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degration by the proteasome (By similarity).  
[https://www.uniprot.org/uniprot/MDM2_XENLA MDM2_XENLA] E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degration by the proteasome (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The p53 tumor suppressor is a potent transcription factor that plays a key role in the regulation of cellular responses to stress. It is controlled by its negative regulator MDM2, which binds directly to p53 and inhibits its transcriptional activity. MDM2 also targets p53 for degradation by the proteasome. Many tumors produce high levels of MDM2, thereby impairing p53 function. Restoration of p53 activity by inhibiting the p53-MDM2 interaction may represent a novel approach to cancer treatment. RG7112 (2g) is the first clinical small-molecule MDM2 inhibitor designed to occupy the p53-binding pocket of MDM2. In cancer cells expressing wild-type p53, RG7112 stabilizes p53 and activates the p53 pathway, leading to cell cycle arrest, apoptosis, and inhibition or regression of human tumor xenografts.
 
Discovery of RG7112: A Small-Molecule MDM2 Inhibitor in Clinical Development.,Vu B, Wovkulich P, Pizzolato G, Lovey A, Ding Q, Jiang N, Liu JJ, Zhao C, Glenn K, Wen Y, Tovar C, Packman K, Vassilev L, Graves B ACS Med Chem Lett. 2013 Apr 2;4(5):466-9. doi: 10.1021/ml4000657. eCollection, 2013 May 9. PMID:24900694<ref>PMID:24900694</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4j3e" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[MDM2|MDM2]]
*[[MDM2 3D structures|MDM2 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: African clawed frog]]
[[Category: Large Structures]]
[[Category: Crowther, R]]
[[Category: Xenopus laevis]]
[[Category: Graves, B J]]
[[Category: Crowther R]]
[[Category: Kammlott, R U]]
[[Category: Graves BJ]]
[[Category: Lukacs, C M]]
[[Category: Kammlott RU]]
[[Category: E3 ubiquitin ligase]]
[[Category: Lukacs CM]]
[[Category: Imidazoline]]
[[Category: Ligase-antagonist complex]]
[[Category: Mdm2]]
[[Category: Nucleus]]
[[Category: P53]]
[[Category: Protein-protein interaction]]

Latest revision as of 15:01, 1 March 2024

The 1.9A crystal structure of humanized Xenopus Mdm2 with nutlin-3aThe 1.9A crystal structure of humanized Xenopus Mdm2 with nutlin-3a

Structural highlights

4j3e is a 1 chain structure with sequence from Xenopus laevis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.91Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MDM2_XENLA E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degration by the proteasome (By similarity).

See Also

4j3e, resolution 1.91Å

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OCA
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