1t4f: Difference between revisions

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-{{Seed}}
-[[Image:1t4f.png|left|200px]]
-<!--
+==Structure of human MDM2 in complex with an optimized p53 peptide==
-The line below this paragraph, containing "STRUCTURE_1t4f", creates the "Structure Box" on the page.
+<StructureSection load='1t4f' size='340' side='right'caption='[[1t4f]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[1t4f]] 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=1T4F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T4F FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-{{STRUCTURE_1t4f|  PDB=1t4f  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1t4f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t4f OCA], [https://pdbe.org/1t4f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t4f RCSB], [https://www.ebi.ac.uk/pdbsum/1t4f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t4f ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[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.
+== Function ==
+[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>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t4/1t4f_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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=1t4f ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+HDM2 binds to an alpha-helical transactivation domain of p53, inhibiting its tumor suppressive functions. A miniaturized thermal denaturation assay was used to screen chemical libraries, resulting in the discovery of a novel series of benzodiazepinedione antagonists of the HDM2-p53 interaction. The X-ray crystal structure of improved antagonists bound to HDM2 reveals their alpha-helix mimetic properties. These optimized molecules increase the transcription of p53 target genes and decrease proliferation of tumor cells expressing wild-type p53.
-===Structure of human MDM2 in complex with an optimized p53 peptide===
+Discovery and cocrystal structure of benzodiazepinedione HDM2 antagonists that activate p53 in cells.,Grasberger BL, Lu T, Schubert C, Parks DJ, Carver TE, Koblish HK, Cummings MD, LaFrance LV, Milkiewicz KL, Calvo RR, Maguire D, Lattanze J, Franks CF, Zhao S, Ramachandren K, Bylebyl GR, Zhang M, Manthey CL, Petrella EC, Pantoliano MW, Deckman IC, Spurlino JC, Maroney AC, Tomczuk BE, Molloy CJ, Bone RF J Med Chem. 2005 Feb 24;48(4):909-12. PMID:15715460<ref>PMID:15715460</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 1t4f" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_15715460}}, adds the Publication Abstract to the page
+*[[MDM2 3D structures|MDM2 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 15715460 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_15715460}}
+__TOC__
+</StructureSection>
-==About this Structure==
-T4F is a 2 chains 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=1T4F OCA].
-==Reference==
-<ref group="xtra">PMID:15715460</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Carver, T E.]]
+[[Category: Large Structures]]
-[[Category: Franks, C F.]]
+[[Category: Carver TE]]
-[[Category: Grasberger, B L.]]
+[[Category: Franks CF]]
-[[Category: Koblish, H K.]]
+[[Category: Grasberger BL]]
-[[Category: LaFrance, L V.]]
+[[Category: Koblish HK]]
-[[Category: Lu, T.]]
+[[Category: LaFrance LV]]
-[[Category: Parks, D J.]]
+[[Category: Lu T]]
-[[Category: Schubert, C.]]
+[[Category: Parks DJ]]
-[[Category: Zhao, S Y.]]
+[[Category: Schubert C]]
-[[Category: Mdm2-p53 peptide complex]]
+[[Category: Zhao SY]]
-[[Category: P53-binding protein mdm2 oncoprotein mdm2 double minute 2 protein hdm2]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 18 07:49:25 2009''