3tu1: Difference between revisions

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-[[Image:3tu1.png|left|200px]]
-{{STRUCTURE_3tu1|  PDB=3tu1  |  SCENE=  }}
+==Exhaustive Fluorine Scanning towards Potent p53-MDM2 Antagonist==
+<StructureSection load='3tu1' size='340' side='right'caption='[[3tu1]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3tu1]] is a 1 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=3TU1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TU1 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.603&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=07G:2-(TERT-BUTYLAMINO)-1-(2-CARBOXY-6-CHLORO-1H-INDOL-3-YL)-1-[(3,4-DIFLUOROBENZYL)(FORMYL)AMINO]-2-OXOETHYLIUM'>07G</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3tu1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tu1 OCA], [https://pdbe.org/3tu1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tu1 RCSB], [https://www.ebi.ac.uk/pdbsum/3tu1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tu1 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>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Fluorine dance: We discovered potent p53-Mdm2 antagonists by systematically varying the fluorine substitution pattern around a benzyl group that undergoes stacking interactions with His 96 of Mdm2. The potency of the optimized enantiomer (S)-7 e is &gt;50-fold better than the worst compound of the series. All compounds were efficiently synthesized by Ugi multicomponent reaction chemistry.
-===Exhaustive Fluorine Scanning towards Potent p53-MDM2 Antagonist===
+Exhaustive Fluorine Scanning toward Potent p53-Mdm2 Antagonists.,Huang Y, Wolf S, Koes D, Popowicz GM, Camacho CJ, Holak TA, Domling A ChemMedChem. 2012 Jan 2;7(1):49-52. doi: 10.1002/cmdc.201100428. Epub 2011, Sep 27. PMID:21954050<ref>PMID:21954050</ref>
-{{ABSTRACT_PUBMED_21954050}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 3tu1" style="background-color:#fffaf0;"></div>
-[[3tu1]] is a 1 chain structure with sequence 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=3TU1 OCA].
 ==See Also==
-*[[MDM2|MDM2]]
+*[[MDM2 3D structures|MDM2 3D structures]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:021954050</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Camacho, C J.]]
+[[Category: Large Structures]]
-[[Category: Doemling, A.]]
+[[Category: Camacho CJ]]
-[[Category: Holak, T A.]]
+[[Category: Doemling A]]
-[[Category: Huang, Y.]]
+[[Category: Holak TA]]
-[[Category: Koes, D.]]
+[[Category: Huang Y]]
-[[Category: Popowicz, G M.]]
+[[Category: Koes D]]
-[[Category: Wolf, S.]]
+[[Category: Popowicz GM]]
-[[Category: Double minute 2 protein]]
+[[Category: Wolf S]]
-[[Category: Hdm2]]
-[[Category: Ligase]]
-[[Category: Nucleus]]
-[[Category: Oncoprotein]]
-[[Category: Oncoprotein mdm2]]
-[[Category: P53]]
-[[Category: P53-binding protein mdm2]]