5z02: Difference between revisions
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==Crystal structure of HIS6-tagged Mdm2 with nutlin-3a== | |||
<StructureSection load='5z02' size='340' side='right'caption='[[5z02]], [[Resolution|resolution]] 1.35Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5z02]] 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=5Z02 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5Z02 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]] 1.35Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NUT:4-({(4S,5R)-4,5-BIS(4-CHLOROPHENYL)-2-[4-METHOXY-2-(PROPAN-2-YLOXY)PHENYL]-4,5-DIHYDRO-1H-IMIDAZOL-1-YL}CARBONYL)PIPERAZIN-2-ONE'>NUT</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=5z02 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z02 OCA], [https://pdbe.org/5z02 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5z02 RCSB], [https://www.ebi.ac.uk/pdbsum/5z02 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5z02 ProSAT]</span></td></tr> | |||
</table> | |||
== 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 == | |||
[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> | |||
==See Also== | |||
*[[MDM2 3D structures|MDM2 3D structures]] | |||
== References == | |||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: Chen | </StructureSection> | ||
[[Category: Cheng | [[Category: Homo sapiens]] | ||
[[Category: Su | [[Category: Large Structures]] | ||
[[Category: Chen R]] | |||
[[Category: Cheng XY]] | |||
[[Category: Pi N]] | |||
[[Category: Su ZD]] | |||
Latest revision as of 08:42, 22 November 2023
Crystal structure of HIS6-tagged Mdm2 with nutlin-3a
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