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3tj2
From Proteopedia
(Difference between revisions)
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| - | + | ==Structure of a novel submicromolar MDM2 inhibitor== | |
| - | === | + | <StructureSection load='3tj2' size='340' side='right' caption='[[3tj2]], [[Resolution|resolution]] 2.10Å' scene=''> |
| - | + | == Structural highlights == | |
| - | ==Disease== | + | <table><tr><td colspan='2'>[[3tj2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TJ2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TJ2 FirstGlance]. <br> |
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=TJ2:3-{(1S)-2-(TERT-BUTYLAMINO)-1-[(4-CHLOROBENZYL)(FORMYL)AMINO]-2-OXOETHYL}-6-CHLORO-1H-INDOLE-2-CARBOXYLIC+ACID'>TJ2</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ycr|1ycr]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MDM2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3tj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tj2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tj2 RCSB], [http://www.ebi.ac.uk/pdbsum/3tj2 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
[[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. | [[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. | ||
| + | == Function == | ||
| + | [[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> | ||
| - | == | + | ==See Also== |
| - | [[ | + | *[[MDM2|MDM2]] |
| - | + | == References == | |
| - | + | <references/> | |
| - | + | __TOC__ | |
| - | + | </StructureSection> | |
| - | == | + | |
| - | <references | + | |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: Doemling, A | + | [[Category: Doemling, A]] |
| - | [[Category: Goda, S | + | [[Category: Goda, S]] |
| - | [[Category: Holak, T A | + | [[Category: Holak, T A]] |
| - | [[Category: Huang, Y | + | [[Category: Huang, Y]] |
| - | [[Category: Popowicz, G M | + | [[Category: Popowicz, G M]] |
| - | [[Category: Wolf, S | + | [[Category: Wolf, S]] |
[[Category: Cell cycle control]] | [[Category: Cell cycle control]] | ||
[[Category: Dna repair]] | [[Category: Dna repair]] | ||
Revision as of 07:12, 21 December 2014
Structure of a novel submicromolar MDM2 inhibitor
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