3v3b: Difference between revisions

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-[[Image:3v3b.png|left|200px]]
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+==Structure of the Stapled p53 Peptide Bound to Mdm2==
-The line below this paragraph, containing "STRUCTURE_3v3b", creates the "Structure Box" on the page.
+<StructureSection load='3v3b' size='340' side='right'caption='[[3v3b]], [[Resolution|resolution]] 2.00&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'>[[3v3b]] is a 4 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=3V3B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3V3B 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]] 2&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0EH:(2R)-2-AMINO-2-METHYLNONANOIC+ACID'>0EH</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MK8:2-METHYL-L-NORLEUCINE'>MK8</scene></td></tr>
-{{STRUCTURE_3v3b|  PDB=3v3b  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3v3b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v3b OCA], [https://pdbe.org/3v3b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3v3b RCSB], [https://www.ebi.ac.uk/pdbsum/3v3b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3v3b 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 ==
+Mdm2 is a major negative regulator of the tumor suppressor p53 protein, a protein that plays a crucial role in maintaining genome integrity. Inactivation of p53 is the most prevalent defect in human cancers. Inhibitors of the Mdm2-p53 interaction that restore the functional p53 constitute potential nongenotoxic anticancer agents with a novel mode of action. We present here a 2.0 A resolution structure of the Mdm2 protein with a bound stapled p53 peptide. Such peptides, which are conformationally and proteolytically stabilized with all-hydrocarbon staples, are an emerging class of biologics that are capable of disrupting protein-protein interactions and thus have broad therapeutic potential. The structure represents the first crystal structure of an i, i + 7 stapled peptide bound to its target and reveals that rather than acting solely as a passive conformational brace, a staple can intimately interact with the surface of a protein and augment the binding interface.
-===Structure of the Stapled p53 Peptide Bound to Mdm2===
+Structure of the Stapled p53 Peptide Bound to Mdm2.,Baek S, Kutchukian PS, Verdine GL, Huber R, Holak TA, Lee KW, Popowicz GM J Am Chem Soc. 2012 Jan 11;134(1):103-6. Epub 2011 Dec 14. PMID:22148351<ref>PMID:22148351</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3v3b" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_22148351}}, adds the Publication Abstract to the page
+*[[MDM2 3D structures|MDM2 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 22148351 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_22148351}}
+__TOC__
+</StructureSection>
-==About this Structure==
-[[3v3b]] is a 4 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=3V3B OCA].
-==Reference==
-<ref group="xtra">PMID:022148351</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Baek, S.]]
+[[Category: Large Structures]]
-[[Category: Holak, T A.]]
+[[Category: Baek S]]
-[[Category: Huber, R.]]
+[[Category: Holak TA]]
-[[Category: Kutchukian, P S.]]
+[[Category: Huber R]]
-[[Category: Popowicz, G M.]]
+[[Category: Ki Won L]]
-[[Category: Verdine, G L.]]
+[[Category: Kutchukian PS]]
-[[Category: Won, L Ki.]]
+[[Category: Popowicz GM]]
-[[Category: Aliphatic staple]]
+[[Category: Verdine GL]]
-[[Category: Cancer]]
-[[Category: Cell cycle]]
-[[Category: Dna repair]]
-[[Category: Ligase-ligase inhibitor complex]]
-[[Category: Oncoprotein]]
-[[Category: P53-derived peptide]]