1t4e
From Proteopedia
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==Structure of Human MDM2 in complex with a Benzodiazepine Inhibitor== | ==Structure of Human MDM2 in complex with a Benzodiazepine Inhibitor== | ||
| - | <StructureSection load='1t4e' size='340' side='right' caption='[[1t4e]], [[Resolution|resolution]] 2.60Å' scene=''> | + | <StructureSection load='1t4e' size='340' side='right'caption='[[1t4e]], [[Resolution|resolution]] 2.60Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[1t4e]] is a 2 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[1t4e]] is a 2 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=1T4E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T4E FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DIZ:(4-CHLOROPHENYL)[3-(4-CHLOROPHENYL)-7-IODO-2,5-DIOXO-1,2,3,5-TETRAHYDRO-4H-1,4-BENZODIAZEPIN-4-YL]ACETIC+ACID'>DIZ</scene> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DIZ:(4-CHLOROPHENYL)[3-(4-CHLOROPHENYL)-7-IODO-2,5-DIOXO-1,2,3,5-TETRAHYDRO-4H-1,4-BENZODIAZEPIN-4-YL]ACETIC+ACID'>DIZ</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=1t4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t4e OCA], [https://pdbe.org/1t4e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t4e RCSB], [https://www.ebi.ac.uk/pdbsum/1t4e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t4e ProSAT]</span></td></tr> | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | |
</table> | </table> | ||
== Disease == | == Disease == | ||
| - | [ | + | [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. |
== Function == | == Function == | ||
| - | [ | + | [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> |
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t4/1t4e_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t4/1t4e_consurf.spt"</scriptWhenChecked> |
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
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==See Also== | ==See Also== | ||
| - | *[[MDM2|MDM2]] | + | *[[MDM2 3D structures|MDM2 3D structures]] |
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: Carver | + | [[Category: Large Structures]] |
| - | [[Category: Franks | + | [[Category: Carver TE]] |
| - | [[Category: Grasberger | + | [[Category: Franks CF]] |
| - | [[Category: Koblish | + | [[Category: Grasberger BL]] |
| - | [[Category: LaFrance | + | [[Category: Koblish HK]] |
| - | [[Category: Lu | + | [[Category: LaFrance LV]] |
| - | [[Category: Parks | + | [[Category: Lu T]] |
| - | [[Category: Schubert | + | [[Category: Parks DJ]] |
| - | [[Category: Zhao | + | [[Category: Schubert C]] |
| - | + | [[Category: Zhao SY]] | |
| - | + | ||
Current revision
Structure of Human MDM2 in complex with a Benzodiazepine Inhibitor
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Categories: Homo sapiens | Large Structures | Carver TE | Franks CF | Grasberger BL | Koblish HK | LaFrance LV | Lu T | Parks DJ | Schubert C | Zhao SY
