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3lnj

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{{Seed}}
 
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[[Image:3lnj.png|left|200px]]
 
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<!--
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==Crystal structure of human MDM2 in complex with D-peptide inhibitor (DPMI-alpha)==
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The line below this paragraph, containing "STRUCTURE_3lnj", creates the "Structure Box" on the page.
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<StructureSection load='3lnj' size='340' side='right'caption='[[3lnj]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3lnj]] is a 6 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=3LNJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LNJ FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 2.4&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=DAR:D-ARGININE'>DAR</scene>, <scene name='pdbligand=DGL:D-GLUTAMIC+ACID'>DGL</scene>, <scene name='pdbligand=DLE:D-LEUCINE'>DLE</scene>, <scene name='pdbligand=DLY:D-LYSINE'>DLY</scene>, <scene name='pdbligand=DSG:D-ASPARAGINE'>DSG</scene>, <scene name='pdbligand=DTH:D-THREONINE'>DTH</scene>, <scene name='pdbligand=DTR:D-TRYPTOPHAN'>DTR</scene>, <scene name='pdbligand=DTY:D-TYROSINE'>DTY</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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{{STRUCTURE_3lnj| PDB=3lnj | SCENE= }}
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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=3lnj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lnj OCA], [https://pdbe.org/3lnj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lnj RCSB], [https://www.ebi.ac.uk/pdbsum/3lnj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lnj ProSAT]</span></td></tr>
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</table>
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== Disease ==
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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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== 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/ln/3lnj_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=3lnj ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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[Image: see text] Throwing tumors a left hook punch: The oncoprotein MDM2 negatively regulates the activity and stability of the tumor suppressor protein p53, and is an important molecular target for anticancer therapy. Mirror image phage display identifies a high-affinity D-peptide ligand of MDM2 that can be developed into a potent and protease-resistant p53 activator with potential antitumor activity.
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===Crystal structure of human MDM2 in complex with D-peptide inhibitor (DPMI-alpha)===
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A left-handed solution to peptide inhibition of the p53-MDM2 interaction.,Liu M, Pazgier M, Li C, Yuan W, Li C, Lu W Angew Chem Int Ed Engl. 2010 May 10;49(21):3649-52. doi: 10.1002/anie.201000329. PMID:20449836<ref>PMID:20449836</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3lnj" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_20226197}}, adds the Publication Abstract to the page
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*[[MDM2 3D structures|MDM2 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 20226197 is the PubMed ID number.
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== References ==
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-->
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<references/>
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{{ABSTRACT_PUBMED_20226197}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[Category: Homo sapiens]]
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3LNJ is a 6 chains structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LNJ OCA].
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[[Category: Large Structures]]
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[[Category: Lu W]]
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==Reference==
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[[Category: Pazgier M]]
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<ref group="xtra">PMID:20226197</ref><references group="xtra"/>
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[[Category: Lu, W.]]
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[[Category: Pazgier, M.]]
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[[Category: Alternative splicing]]
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[[Category: Cytoplasm]]
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[[Category: D-peptide activator of mdm2]]
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[[Category: Host-virus interaction]]
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[[Category: Ligase]]
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[[Category: Ligase-ligase inhibitor complex]]
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[[Category: Mdm2]]
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[[Category: Mdm2-d-peptide complex]]
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[[Category: Metal-binding]]
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[[Category: Nucleus]]
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[[Category: P53 binding domain]]
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[[Category: Phosphoprotein]]
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[[Category: Proto-oncogene]]
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[[Category: Ubl conjugation]]
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[[Category: Ubl conjugation pathway]]
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[[Category: Zinc]]
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[[Category: Zinc-finger]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 28 10:57:12 2010''
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Current revision

Crystal structure of human MDM2 in complex with D-peptide inhibitor (DPMI-alpha)

PDB ID 3lnj

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