3oni: Difference between revisions

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-[[Image:3oni.png|left|200px]]
-<!--
+==Crystal Structure of the second bromodomain of human BRD2 in complex with the inhibitor JQ1==
-The line below this paragraph, containing "STRUCTURE_3oni", creates the "Structure Box" on the page.
+<StructureSection load='3oni' size='340' side='right'caption='[[3oni]], [[Resolution|resolution]] 1.61&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'>[[3oni]] 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=3ONI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ONI 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]] 1.61&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=JQ1:(6S)-6-(2-TERT-BUTOXY-2-OXOETHYL)-4-(4-CHLOROPHENYL)-2,3,9-TRIMETHYL-6,7-DIHYDROTHIENO[3,2-F][1,2,4]TRIAZOLO[4,3-A][1,4]DIAZEPIN-10-IUM'>JQ1</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr>
-{{STRUCTURE_3oni|  PDB=3oni  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3oni FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oni OCA], [https://pdbe.org/3oni PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3oni RCSB], [https://www.ebi.ac.uk/pdbsum/3oni PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3oni ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/BRD2_HUMAN BRD2_HUMAN] May play a role in spermatogenesis or folliculogenesis (By similarity). Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling. Regulates transcription of the CCND1 gene. Plays a role in nucleosome assembly.<ref>PMID:18406326</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/on/3oni_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=3oni ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Epigenetic proteins are intently pursued targets in ligand discovery. So far, successful efforts have been limited to chromatin modifying enzymes, or so-called epigenetic 'writers' and 'erasers'. Potent inhibitors of histone binding modules have not yet been described. Here we report a cell-permeable small molecule (JQ1) that binds competitively to acetyl-lysine recognition motifs, or bromodomains. High potency and specificity towards a subset of human bromodomains is explained by co-crystal structures with bromodomain and extra-terminal (BET) family member BRD4, revealing excellent shape complementarity with the acetyl-lysine binding cavity. Recurrent translocation of BRD4 is observed in a genetically-defined, incurable subtype of human squamous carcinoma. Competitive binding by JQ1 displaces the BRD4 fusion oncoprotein from chromatin, prompting squamous differentiation and specific antiproliferative effects in BRD4-dependent cell lines and patient-derived xenograft models. These data establish proof-of-concept for targeting protein-protein interactions of epigenetic 'readers', and provide a versatile chemical scaffold for the development of chemical probes more broadly throughout the bromodomain family.
-===Crystal Structure of the second bromodomain of humand BRD2 in complex with the inhibitor JQ1===
+Selective inhibition of BET bromodomains.,Filippakopoulos P, Qi J, Picaud S, Shen Y, Smith WB, Fedorov O, Morse EM, Keates T, Hickman TT, Felletar I, Philpott M, Munro S, McKeown MR, Wang Y, Christie AL, West N, Cameron MJ, Schwartz B, Heightman TD, La Thangue N, French CA, Wiest O, Kung AL, Knapp S, Bradner JE Nature. 2010 Sep 24. PMID:20871596<ref>PMID:20871596</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3oni" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_20871596}}, adds the Publication Abstract to the page
+*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 20871596 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_20871596}}
+__TOC__
+</StructureSection>
-==About this Structure==
-[[3oni]] 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=3ONI OCA].
-==Reference==
-<ref group="xtra">PMID:20871596</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Arrowsmith, C H.]]
+[[Category: Large Structures]]
-[[Category: Bountra, C.]]
+[[Category: Arrowsmith CH]]
-[[Category: Bradner, J E.]]
+[[Category: Bountra C]]
-[[Category: Delft, F von.]]
+[[Category: Bradner JE]]
-[[Category: Edwards, A M.]]
+[[Category: Edwards AM]]
-[[Category: Fedorov, O.]]
+[[Category: Fedorov O]]
-[[Category: Filippakopoulos, P.]]
+[[Category: Filippakopoulos P]]
-[[Category: Picaud, S.]]
+[[Category: Picaud S]]
-[[Category: SGC, Structural Genomics Consortium.]]
+[[Category: Weigelt J]]
-[[Category: Weigelt, J.]]
+[[Category: Von Delft F]]