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3tu1
From Proteopedia
(Difference between revisions)
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==Exhaustive Fluorine Scanning towards Potent p53-MDM2 Antagonist== | ==Exhaustive Fluorine Scanning towards Potent p53-MDM2 Antagonist== | ||
| - | <StructureSection load='3tu1' size='340' side='right' caption='[[3tu1]], [[Resolution|resolution]] 1.60Å' scene=''> | + | <StructureSection load='3tu1' size='340' side='right'caption='[[3tu1]], [[Resolution|resolution]] 1.60Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[3tu1]] is a 1 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[3tu1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TU1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TU1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=07G:2-(TERT-BUTYLAMINO)-1-(2-CARBOXY-6-CHLORO-1H-INDOL-3-YL)-1-[(3,4-DIFLUOROBENZYL)(FORMYL)AMINO]-2-OXOETHYLIUM'>07G</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=07G:2-(TERT-BUTYLAMINO)-1-(2-CARBOXY-6-CHLORO-1H-INDOL-3-YL)-1-[(3,4-DIFLUOROBENZYL)(FORMYL)AMINO]-2-OXOETHYLIUM'>07G</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MDM2 ([ | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MDM2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3tu1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tu1 OCA], [https://pdbe.org/3tu1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tu1 RCSB], [https://www.ebi.ac.uk/pdbsum/3tu1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tu1 ProSAT]</span></td></tr> |
</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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</div> | </div> | ||
<div class="pdbe-citations 3tu1" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 3tu1" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[MDM2 3D structures|MDM2 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Human]] | [[Category: Human]] | ||
| + | [[Category: Large Structures]] | ||
[[Category: Camacho, C J]] | [[Category: Camacho, C J]] | ||
[[Category: Doemling, A]] | [[Category: Doemling, A]] | ||
Revision as of 05:45, 13 July 2022
Exhaustive Fluorine Scanning towards Potent p53-MDM2 Antagonist
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Categories: Human | Large Structures | Camacho, C J | Doemling, A | Holak, T A | Huang, Y | Koes, D | Popowicz, G M | Wolf, S | Double minute 2 protein | Hdm2 | Ligase | Nucleus | Oncoprotein | Oncoprotein mdm2 | P53 | P53-binding protein mdm2
