2gv2: Difference between revisions
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<StructureSection load='2gv2' size='340' side='right' caption='[[2gv2]], [[Resolution|resolution]] 1.80Å' scene=''> | <StructureSection load='2gv2' size='340' side='right' caption='[[2gv2]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2gv2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2gv2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GV2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2GV2 FirstGlance]. <br> | ||
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=1AC:1-AMINOCYCLOPROPANECARBOXYLIC+ACID'>1AC</scene>, <scene name='pdbligand=6CW:6-CHLORO-L-TRYPTOPHAN'>6CW</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=AIB:ALPHA-AMINOISOBUTYRIC+ACID'>AIB</scene>, <scene name='pdbligand=PM3:2-AMINO-3-(4-PHOSPHONOMETHYL-PHENYL)-PROPIONIC+ACID'>PM3</scene></td></tr> | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=1AC:1-AMINOCYCLOPROPANECARBOXYLIC+ACID'>1AC</scene>, <scene name='pdbligand=6CW:6-CHLORO-L-TRYPTOPHAN'>6CW</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=AIB:ALPHA-AMINOISOBUTYRIC+ACID'>AIB</scene>, <scene name='pdbligand=PM3:2-AMINO-3-(4-PHOSPHONOMETHYL-PHENYL)-PROPIONIC+ACID'>PM3</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ycr|1ycr]], [[1t4f|1t4f]], [[1t4e|1t4e]], [[1rv1|1rv1]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ycr|1ycr]], [[1t4f|1t4f]], [[1t4e|1t4e]], [[1rv1|1rv1]]</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 | <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 HUMAN])</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=2gv2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gv2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2gv2 RCSB], [http://www.ebi.ac.uk/pdbsum/2gv2 PDBsum]</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=2gv2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gv2 OCA], [http://pdbe.org/2gv2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2gv2 RCSB], [http://www.ebi.ac.uk/pdbsum/2gv2 PDBsum]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 2gv2" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Human]] | ||
[[Category: Sakurai, K]] | [[Category: Sakurai, K]] | ||
[[Category: Schubert, C]] | [[Category: Schubert, C]] | ||
[[Category: Ligase]] | [[Category: Ligase]] | ||
[[Category: Optimized protein-protein interaction. synthetic peptide. alpha helix binding protein]] | [[Category: Optimized protein-protein interaction. synthetic peptide. alpha helix binding protein]] | ||
Revision as of 09:23, 10 September 2015
MDM2 in complex with an 8-mer p53 peptide analogueMDM2 in complex with an 8-mer p53 peptide analogue
Structural highlights
Disease[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[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.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe most potent inhibitor of the p53-MDM2 interaction reported to date is an 8-mer p53 peptide analogue (Novartis peptide), which contains 6-chlorotryptophane (Cl-Trp) and phosphonomethylphenylalanine (Pmp) as key residues for the enhanced activity. We report here a crystal structure of the co-complex between MDM2 and the Novartis peptide solved at 1.8 A resolution. The structural basis for the role of the two aromatic residues are delineated by comparing the present structure with crystal structures of the MDM2 co-complex bound to other inhibitors including the wt-p53 peptide itself. Crystallographic analysis of an 8-mer p53 peptide analogue complexed with MDM2.,Sakurai K, Schubert C, Kahne D J Am Chem Soc. 2006 Aug 30;128(34):11000-1. PMID:16925398[12] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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