6h22
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of Mdm2 bound to a stapled peptide== | |
| - | + | <StructureSection load='6h22' size='340' side='right'caption='[[6h22]], [[Resolution|resolution]] 2.01Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[6h22]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6H22 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6H22 FirstGlance]. <br> | |
| - | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FL5:12-(dimethylamino)-3,10-diethyl-N,N,N-trimethyl-3,10-dihydrodibenzo[3,4 7,8]cycloocta[1,2-d 5,6-d]bis([1,2,3]triazole)-5-aminium'>FL5</scene></td></tr> | |
| - | [[Category: | + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> |
| - | [[Category: | + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RING-type_E3_ubiquitin_transferase RING-type E3 ubiquitin transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.27 2.3.2.27] </span></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=6h22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6h22 OCA], [http://pdbe.org/6h22 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6h22 RCSB], [http://www.ebi.ac.uk/pdbsum/6h22 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6h22 ProSAT]</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. | ||
| + | == 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> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: RING-type E3 ubiquitin transferase]] | ||
[[Category: Hyvonen, M]] | [[Category: Hyvonen, M]] | ||
[[Category: Sharma, K]] | [[Category: Sharma, K]] | ||
| + | [[Category: Spring, D R]] | ||
[[Category: Wang, X]] | [[Category: Wang, X]] | ||
| + | [[Category: E3-ligase]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Ligase]] | ||
| + | [[Category: Stapled peptide]] | ||
Revision as of 06:13, 31 July 2019
Crystal structure of Mdm2 bound to a stapled peptide
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