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4occ

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{{STRUCTURE_4occ| PDB=4occ | SCENE= }}
 
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===co-crystal structure of MDM2(17-111) in complex with compound 48===
 
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{{ABSTRACT_PUBMED_24601644}}
 
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==Disease==
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==co-crystal structure of MDM2(17-111) in complex with compound 48==
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[[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.
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<StructureSection load='4occ' size='340' side='right'caption='[[4occ]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4occ]] is a 3 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=4OCC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4OCC FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2TZ:[(2R,5R,6R)-4-[(2S)-1-(TERT-BUTYLSULFONYL)BUTAN-2-YL]-6-(3-CHLOROPHENYL)-5-(4-CHLOROPHENYL)-3-OXOMORPHOLIN-2-YL]ACETIC+ACID'>2TZ</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4occ FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4occ OCA], [https://pdbe.org/4occ PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4occ RCSB], [https://www.ebi.ac.uk/pdbsum/4occ PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4occ ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://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.
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== Function ==
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[https://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>
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==Function==
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==See Also==
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[[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>
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*[[MDM2 3D structures|MDM2 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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[[4occ]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OCC OCA].
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__TOC__
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</StructureSection>
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==Reference==
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[[Category: Homo sapiens]]
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<ref group="xtra">PMID:024601644</ref><references group="xtra"/><references/>
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[[Category: Large Structures]]
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[[Category: Huang, X.]]
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[[Category: Huang X]]
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[[Category: Inhibitor]]
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[[Category: Ligase-ligase inhibitor complex]]
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[[Category: Mdm2]]
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[[Category: P53]]
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[[Category: Protein-protein interaction]]
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Current revision

co-crystal structure of MDM2(17-111) in complex with compound 48

PDB ID 4occ

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