1ycr

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[[Image:1ycr.jpg|left|200px]]
 
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{{Structure
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==MDM2 BOUND TO THE TRANSACTIVATION DOMAIN OF P53==
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|PDB= 1ycr |SIZE=350|CAPTION= <scene name='initialview01'>1ycr</scene>, resolution 2.6&Aring;
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<StructureSection load='1ycr' size='340' side='right'caption='[[1ycr]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND=
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<table><tr><td colspan='2'>[[1ycr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YCR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YCR FirstGlance]. <br>
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|ACTIVITY=
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
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|GENE=
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ycr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ycr OCA], [https://pdbe.org/1ycr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ycr RCSB], [https://www.ebi.ac.uk/pdbsum/1ycr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ycr ProSAT]</span></td></tr>
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|DOMAIN=
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</table>
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|RELATEDENTRY=
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== Disease ==
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ycr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ycr OCA], [http://www.ebi.ac.uk/pdbsum/1ycr PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ycr RCSB]</span>
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[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.
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}}
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/yc/1ycr_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ycr ConSurf].
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<div style="clear:both"></div>
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'''MDM2 BOUND TO THE TRANSACTIVATION DOMAIN OF P53'''
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==See Also==
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*[[MDM2 3D structures|MDM2 3D structures]]
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*[[P53 3D structures|P53 3D structures]]
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==Overview==
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== References ==
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The MDM2 oncoprotein is a cellular inhibitor of the p53 tumor suppressor in that it can bind the transactivation domain of p53 and downregulate its ability to activate transcription. In certain cancers, MDM2 amplification is a common event and contributes to the inactivation of p53. The crystal structure of the 109-residue amino-terminal domain of MDM2 bound to a 15-residue transactivation domain peptide of p53 revealed that MDM2 has a deep hydrophobic cleft on which the p53 peptide binds as an amphipathic alpha helix. The interface relies on the steric complementarity between the MDM2 cleft and the hydrophobic face of the p53 alpha helix and, in particular, on a triad of p53 amino acids-Phe19, Trp23, and Leu26-which insert deep into the MDM2 cleft. These same p53 residues are also involved in transactivation, supporting the hypothesis that MDM2 inactivates p53 by concealing its transactivation domain. The structure also suggests that the amphipathic alpha helix may be a common structural motif in the binding of a diverse family of transactivation factors to the TATA-binding protein-associated factors.
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<references/>
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__TOC__
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==About this Structure==
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</StructureSection>
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1YCR is a [[Protein complex]] structure of sequences 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=1YCR OCA].
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==Reference==
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Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain., Kussie PH, Gorina S, Marechal V, Elenbaas B, Moreau J, Levine AJ, Pavletich NP, Science. 1996 Nov 8;274(5289):948-53. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8875929 8875929]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Kussie, P H.]]
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[[Category: Kussie PH]]
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[[Category: Pavletich, N P.]]
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[[Category: Pavletich NP]]
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[[Category: activator]]
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[[Category: anti-oncogene]]
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[[Category: complex (oncogene protein/peptide)]]
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[[Category: dna-binding]]
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[[Category: nuclear protein]]
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[[Category: phosphorylation]]
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[[Category: transcription regulation]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:03:15 2008''
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Current revision

MDM2 BOUND TO THE TRANSACTIVATION DOMAIN OF P53

PDB ID 1ycr

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