View source for 4lwt


==The 1.6A Crystal Structure of Humanized Xenopus MDM2 with RO5027344==
<StructureSection load='4lwt' size='340' side='right' caption='[[4lwt]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4lwt]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LWT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LWT FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=20Q:(3S)-3-[(3R)-1-ACETYLPIPERIDIN-3-YL]-6-CHLORO-3-(3-CHLOROBENZYL)-1,3-DIHYDRO-2H-INDOL-2-ONE'>20Q</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4lwu|4lwu]], [[4lwv|4lwv]]</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=4lwt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lwt OCA], [http://pdbe.org/4lwt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lwt RCSB], [http://www.ebi.ac.uk/pdbsum/4lwt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lwt ProSAT]</span></td></tr>
</table>
== 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). 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The field of small-molecule inhibitors of protein-protein interactions is rapidly advancing and the specific area of inhibitors of the p53/MDM2 interaction is a prime example. Several groups have published on this topic and multiple compounds are in various stages of clinical development. Building on the strength of the discovery of RG7112, a Nutlin imidazoline-based compound, and RG7388, a pyrrolidine-based compound, we have developed additional scaffolds that provide opportunities for future development. Here, we report the discovery and optimization of a highly potent and selective series of spiroindolinone small-molecule MDM2 inhibitors, culminating in RO8994.

Discovery of potent and selective spiroindolinone MDM2 inhibitor, RO8994, for cancer therapy.,Zhang Z, Ding Q, Liu JJ, Zhang J, Jiang N, Chu XJ, Bartkovitz D, Luk KC, Janson C, Tovar C, Filipovic ZM, Higgins B, Glenn K, Packman K, Vassilev LT, Graves B Bioorg Med Chem. 2014 Jun 11. pii: S0968-0896(14)00431-3. doi:, 10.1016/j.bmc.2014.05.072. PMID:24997575<ref>PMID:24997575</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4lwt" style="background-color:#fffaf0;"></div>

==See Also==
*[[MDM2|MDM2]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Graves, B J]]
[[Category: Kammlott, U]]
[[Category: Lukacs, C]]
[[Category: E3 ubiquitin ligase]]
[[Category: Indolinone]]
[[Category: Ligase-ligase inhibitor complex]]
[[Category: Mdm2]]
[[Category: Nucleus]]
[[Category: P53]]