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3lbj
From Proteopedia
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| - | [[Image:3lbj.png|left|200px]] | ||
| - | + | ==Structure of human MDMX protein in complex with a small molecule inhibitor== | |
| + | <StructureSection load='3lbj' size='340' side='right'caption='[[3lbj]], [[Resolution|resolution]] 1.50Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3lbj]] is a 1 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=3LBJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LBJ 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]] 1.5Å</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=WW8:N-[(3S)-1-({6-CHLORO-3-[1-(4-CHLOROBENZYL)-4-PHENYL-1H-IMIDAZOL-5-YL]-1H-INDOL-2-YL}CARBONYL)PYRROLIDIN-3-YL]-N,N,N-TRIMETHYLPROPANE-1,3-DIAMINE'>WW8</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=3lbj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lbj OCA], [https://pdbe.org/3lbj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lbj RCSB], [https://www.ebi.ac.uk/pdbsum/3lbj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lbj ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/MDM4_HUMAN MDM4_HUMAN] Inhibits p53/TP53- and TP73/p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Inhibits degradation of MDM2. Can reverse MDM2-targeted degradation of TP53 while maintaining suppression of TP53 transactivation and apoptotic functions.<ref>PMID:16163388</ref> <ref>PMID:16511572</ref> | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lb/3lbj_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3lbj ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Intensive anticancer drug discovery efforts have been made to develop small molecule inhibitors of the p53-MDM2 and p53-MDMX interactions. We present here the structures of the most potent inhibitors bound to MDM2 and MDMX that are based on the new imidazo-indole scaffold. In addition, the structure of the recently reported spiro-oxindole inhibitor bound to MDM2 is described. The structures indicate how the substituents of a small molecule that bind to the three subpockets of the MDM2/X-p53 interaction should be optimized for effective binding to MDM2 and/or MDMX. While the spiro-oxindole inhibitor triggers significant ligand-induced changes in MDM2, the imidazo-indoles share similar binding modes for MDMX and MDM2, but cause only minimal induced-fit changes in the structures of both proteins. Our study includes the first structure of the complex between MDMX and a small molecule and should aid in developing efficient scaffolds for binding to MDMX and/or MDM2. | ||
| - | + | Structures of low molecular weight inhibitors bound to MDMX and MDM2 reveal new approaches for p53-MDMX/MDM2 antagonist drug discovery.,Popowicz GM, Czarna A, Wolf S, Wang K, Wang W, Domling A, Holak TA Cell Cycle. 2010 Mar 15;9(6):1104-11. doi: 10.4161/cc.9.6.10956. Epub 2010 Mar, 15. PMID:20237429<ref>PMID:20237429</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 3lbj" style="background-color:#fffaf0;"></div> | |
| - | + | ||
==See Also== | ==See Also== | ||
*[[MDM4|MDM4]] | *[[MDM4|MDM4]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Czarna A]] |
| - | [[Category: | + | [[Category: Holak TA]] |
| - | [[Category: | + | [[Category: Popowicz GM]] |
| - | [[Category: | + | [[Category: Wolf S]] |
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Current revision
Structure of human MDMX protein in complex with a small molecule inhibitor
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