5vk0
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of human MDM2 in complex with a 12-mer lysine-cysteine side chain dithiocarbamate stapled peptide inhibitor PMI== | |
| - | + | <StructureSection load='5vk0' size='340' side='right' caption='[[5vk0]], [[Resolution|resolution]] 1.80Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[5vk0]] is a 24 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VK0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VK0 FirstGlance]. <br> | |
| - | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> | |
| - | [[Category: | + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=9E7:'>9E7</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> |
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3eqs|3eqs]], [[5vk1|5vk1]]</td></tr> | ||
| + | <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=5vk0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vk0 OCA], [http://pdbe.org/5vk0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vk0 RCSB], [http://www.ebi.ac.uk/pdbsum/5vk0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vk0 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: RING-type E3 ubiquitin transferase]] | ||
| + | [[Category: Gohain, N]] | ||
[[Category: Pazgier, M]] | [[Category: Pazgier, M]] | ||
| - | [[Category: Tolbert, W | + | [[Category: Tolbert, W D]] |
| - | [[Category: | + | [[Category: Host-virus interaction]] |
| + | [[Category: Ligase]] | ||
| + | [[Category: Ligase-ligase inhibitor complex]] | ||
| + | [[Category: Mdm2-peptide inhibitor complex]] | ||
| + | [[Category: Metal-binding]] | ||
| + | [[Category: Nucleus]] | ||
| + | [[Category: Oncoprotein]] | ||
| + | [[Category: Phosphoprotein]] | ||
| + | [[Category: Proto-oncogene]] | ||
| + | [[Category: Stapled peptide]] | ||
| + | [[Category: Ubl conjugation pathway]] | ||
| + | [[Category: Zinc-finger]] | ||
Revision as of 05:24, 25 April 2018
Crystal structure of human MDM2 in complex with a 12-mer lysine-cysteine side chain dithiocarbamate stapled peptide inhibitor PMI
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Categories: RING-type E3 ubiquitin transferase | Gohain, N | Pazgier, M | Tolbert, W D | Host-virus interaction | Ligase | Ligase-ligase inhibitor complex | Mdm2-peptide inhibitor complex | Metal-binding | Nucleus | Oncoprotein | Phosphoprotein | Proto-oncogene | Stapled peptide | Ubl conjugation pathway | Zinc-finger
