View source for 7ahz


==Crystal structure of Western clawed frog MDM2 RING domain homodimer bound to UbcH5B-Ub==
<StructureSection load='7ahz' size='340' side='right'caption='[[7ahz]], [[Resolution|resolution]] 1.82&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ahz]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Xenopus_tropicalis Xenopus tropicalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AHZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AHZ 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]] 1.82&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=7ahz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ahz OCA], [https://pdbe.org/7ahz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ahz RCSB], [https://www.ebi.ac.uk/pdbsum/7ahz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ahz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q6P3Q9_XENTR Q6P3Q9_XENTR] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
As a key regulator of the tumour suppressor protein p53, MDM2 is involved in various types of cancer and has thus been an attractive drug target. So far, small molecule design has primarily focussed on the N-terminal p53-binding domain although on-target toxicity effects have been reported. Targeting the catalytic RING domain of MDM2 resembles an alternative approach to drug MDM2 with the idea to prevent MDM2-mediated ubiquitination of p53 while retaining MDM2's ability to bind p53. The design of RING inhibitors has been limited by the extensive aggregation tendency of the RING domain, making it challenging to undertake co-crystallization attempts with potential inhibitors. Here we compare the purification profiles of the MDM2 RING domain from several species and show that the MDM2 RING domain of other species than human is much less prone to aggregate although the overall structure of the RING domain is conserved. Through sequence comparison and mutagenesis analyses, we identify a single point mutation, G443T, which greatly enhances the dimeric fraction of human MDM2 RING domain during purification. Neither does the mutation alter the structure of the RING domain, nor does it affect E2(UbcH5B)-Ub binding and activity. Hence, MDM2-G443T facilitates studies involving binding partners that would be hampered by the low solubility of the wild-type RING domain. Furthermore, it will be valuable for the development of MDM2 RING inhibitors.

Identification of a Catalytic Active but Non-Aggregating MDM2 RING Domain Variant.,Magnussen HM, Huang DT J Mol Biol. 2021 Mar 5;433(5):166807. doi: 10.1016/j.jmb.2021.166807. Epub 2021 , Jan 13. PMID:33450248<ref>PMID:33450248</ref>

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

==See Also==
*[[MDM2 3D structures|MDM2 3D structures]]
*[[3D structures of ubiquitin conjugating enzyme|3D structures of ubiquitin conjugating enzyme]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Xenopus tropicalis]]
[[Category: Huang DT]]
[[Category: Magnussen HM]]