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{{STRUCTURE_3lbl|  PDB=3lbl  |  SCENE=  }}
==Structure of human MDM2 protein in complex with Mi-63-analog==
===Structure of human MDM2 protein in complex with Mi-63-analog===
<StructureSection load='3lbl' size='340' side='right' caption='[[3lbl]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
 
== Structural highlights ==
==Disease==
<table><tr><td colspan='2'>[[3lbl]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LBL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LBL FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MI6:(2R,3R,4R,5R)-6-CHLORO-4-(3-CHLORO-2-FLUOROPHENYL)-2-(2,2-DIMETHYLPROPYL)-N-(2-MORPHOLIN-4-YLETHYL)-2-OXO-1,2-DIHYDROSPIRO[INDOLE-3,3-PYRROLIDINE]-5-CARBOXAMIDE'>MI6</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ycr|1ycr]], [[3lbj|3lbj]], [[3lbk|3lbk]]</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=9606 Homo sapiens])</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=3lbl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lbl OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3lbl RCSB], [http://www.ebi.ac.uk/pdbsum/3lbl PDBsum]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN]] Note=Seems to be amplified in certain tumors (including soft tissue sarcomas, osteosarcomas and gliomas). A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding.  
[[http://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN]] Note=Seems to be amplified in certain tumors (including soft tissue sarcomas, osteosarcomas and gliomas). A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding.  
 
== Function ==
==Function==
[[http://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN]] E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as an ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and promotes it to proteasomal degradation.<ref>PMID:12821780</ref> <ref>PMID:15053880</ref> <ref>PMID:15195100</ref> <ref>PMID:16337594</ref> <ref>PMID:15632057</ref> <ref>PMID:17290220</ref> <ref>PMID:19098711</ref> <ref>PMID:19219073</ref> <ref>PMID:19965871</ref> <ref>PMID:20858735</ref> <ref>PMID:20173098</ref>
[[http://www.uniprot.org/uniprot/MDM2_HUMAN MDM2_HUMAN]] E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as an ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and promotes it to proteasomal degradation.<ref>PMID:12821780</ref><ref>PMID:15053880</ref><ref>PMID:15195100</ref><ref>PMID:16337594</ref><ref>PMID:15632057</ref><ref>PMID:17290220</ref><ref>PMID:19098711</ref><ref>PMID:19219073</ref><ref>PMID:19965871</ref><ref>PMID:20858735</ref><ref>PMID:20173098</ref>  
== Evolutionary Conservation ==
 
[[Image:Consurf_key_small.gif|200px|right]]
==About this Structure==
Check<jmol>
[[3lbl]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LBL OCA].  
  <jmolCheckbox>
    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lb/3lbl_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/chain_selection.php?pdb_ID=2ata ConSurf].
<div style="clear:both"></div>


==See Also==
==See Also==
*[[MDM2|MDM2]]
*[[MDM2|MDM2]]
 
== References ==
==Reference==
<references/>
<references group="xtra"/><references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Czarna, A.]]
[[Category: Czarna, A]]
[[Category: Holak, T A.]]
[[Category: Holak, T A]]
[[Category: Popowicz, G M.]]
[[Category: Popowicz, G M]]
[[Category: Wolf, S.]]
[[Category: Wolf, S]]
[[Category: Inhibitor]]
[[Category: Inhibitor]]
[[Category: Ligase]]
[[Category: Ligase]]

Revision as of 16:13, 18 December 2014

Structure of human MDM2 protein in complex with Mi-63-analog

3lbl, resolution 1.60Å

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