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4jvr
From Proteopedia
(Difference between revisions)
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==Co-crystal structure of MDM2 with inhibitor (2'S,3R,4'S,5'R)-N-(2-aminoethyl)-6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2,2-dimethylpropyl)-2-oxo-1,2-dihydrospiro[indole-3,3'-pyrrolidine]-5'-carboxamide== | ==Co-crystal structure of MDM2 with inhibitor (2'S,3R,4'S,5'R)-N-(2-aminoethyl)-6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2,2-dimethylpropyl)-2-oxo-1,2-dihydrospiro[indole-3,3'-pyrrolidine]-5'-carboxamide== | ||
| - | <StructureSection load='4jvr' size='340' side='right' caption='[[4jvr]], [[Resolution|resolution]] 1.70Å' scene=''> | + | <StructureSection load='4jvr' size='340' side='right'caption='[[4jvr]], [[Resolution|resolution]] 1.70Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[4jvr]] is a 3 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[4jvr]] 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=4JVR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JVR FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1MT:(2S,3R,4S,5R)-N-(2-AMINOETHYL)-6-CHLORO-4-(3-CHLORO-2-FLUOROPHENYL)-2-(2,2-DIMETHYLPROPYL)-2-OXO-1,2-DIHYDROSPIRO[INDOLE-3,3-PYRROLIDINE]-5-CARBOXAMIDE'>1MT</scene> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1MT:(2S,3R,4S,5R)-N-(2-AMINOETHYL)-6-CHLORO-4-(3-CHLORO-2-FLUOROPHENYL)-2-(2,2-DIMETHYLPROPYL)-2-OXO-1,2-DIHYDROSPIRO[INDOLE-3,3-PYRROLIDINE]-5-CARBOXAMIDE'>1MT</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=4jvr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jvr OCA], [https://pdbe.org/4jvr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jvr RCSB], [https://www.ebi.ac.uk/pdbsum/4jvr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jvr 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> |
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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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: Bartberger | + | [[Category: Large Structures]] |
| - | [[Category: Beck | + | [[Category: Bartberger MD]] |
| - | [[Category: Cannon | + | [[Category: Beck HP]] |
| - | [[Category: Huang | + | [[Category: Cannon J]] |
| - | [[Category: Medina | + | [[Category: Gonzalez-Lopez de Turiso F]] |
| - | [[Category: Oliner | + | [[Category: Huang X]] |
| - | [[Category: Olson | + | [[Category: Medina JC]] |
| - | [[Category: Shaffer | + | [[Category: Oliner JD]] |
| - | [[Category: Sun | + | [[Category: Olson SH]] |
| - | + | [[Category: Shaffer P]] | |
| - | [[Category: Yosup | + | [[Category: Sun D]] |
| - | + | [[Category: Yosup R]] | |
| - | + | ||
| - | + | ||
Revision as of 11:27, 30 November 2022
Co-crystal structure of MDM2 with inhibitor (2'S,3R,4'S,5'R)-N-(2-aminoethyl)-6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2,2-dimethylpropyl)-2-oxo-1,2-dihydrospiro[indole-3,3'-pyrrolidine]-5'-carboxamide
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Categories: Homo sapiens | Large Structures | Bartberger MD | Beck HP | Cannon J | Gonzalez-Lopez de Turiso F | Huang X | Medina JC | Oliner JD | Olson SH | Shaffer P | Sun D | Yosup R
