4o7a: Difference between revisions

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-{{STRUCTURE_4o7a|  PDB=4o7a  |  SCENE=  }}
-===Crystal structure of the first bromodomain of human BRD4 in complex with SB-409514===
-{{ABSTRACT_PUBMED_24568369}}
-==Disease==
+==Crystal structure of the first bromodomain of human BRD4 in complex with SB-409514==
-[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref>
+<StructureSection load='4o7a' size='340' side='right'caption='[[4o7a]], [[Resolution|resolution]] 1.34&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4o7a]] 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=4O7A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4O7A 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]] 1.34&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2RF:3-[(3-CHLORO-4-HYDROXYPHENYL)AMINO]-4-(3-CHLOROPHENYL)-1H-PYRROLE-2,5-DIONE'>2RF</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=4o7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o7a OCA], [https://pdbe.org/4o7a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4o7a RCSB], [https://www.ebi.ac.uk/pdbsum/4o7a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4o7a ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Members of the bromodomain and extra terminal (BET) family of proteins are essential for the recognition of acetylated lysine (KAc) residues in histones and have emerged as promising drug targets in cancer, inflammation, and contraception research. In co-crystallization screening campaigns using the first bromodomain of BRD4 (BRD4-1) against kinase inhibitor libraries, we identified and characterized 14 kinase inhibitors (10 distinct chemical scaffolds) as ligands of the KAc binding site. Among these, the PLK1 inhibitor BI2536 and the JAK2 inhibitor TG101209 displayed strongest inhibitory potential against BRD4 (IC50 = 25 nM and 130 nM, respectively) and high selectivity for BET bromodomains. Comparative structural analysis revealed markedly different binding modes of kinase hinge-binding scaffolds in the KAc binding site, suggesting that BET proteins are potential off-targets of diverse kinase inhibitors. Combined, these findings provide a new structural framework for the rational design of next-generation BET-selective and dual-activity BET-kinase inhibitors.
-==Function==
+Acetyl-lysine Binding Site of Bromodomain-Containing Protein 4 (BRD4) Interacts with Diverse Kinase Inhibitors.,Ember SW, Zhu JY, Olesen SH, Martin MP, Becker A, Berndt N, Georg GI, Schonbrunn E ACS Chem Biol. 2014 Mar 13. PMID:24568369<ref>PMID:24568369</ref>
-[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[4o7a]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O7A OCA].
+</div>
+<div class="pdbe-citations 4o7a" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-<ref group="xtra">PMID:024568369</ref><references group="xtra"/><references/>
+*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]
-[[Category: Ember, S W.]]
+== References ==
-[[Category: Schonbrunn, E.]]
+<references/>
-[[Category: Watts, C.]]
+__TOC__
-[[Category: Zhu, J Y.]]
+</StructureSection>
-[[Category: Bromodomain]]
+[[Category: Homo sapiens]]
-[[Category: Cap]]
+[[Category: Large Structures]]
-[[Category: Cell cycle]]
+[[Category: Ember SW]]
-[[Category: Hunk1]]
+[[Category: Schonbrunn E]]
-[[Category: Inhibitor]]
+[[Category: Watts C]]
-[[Category: Mcap]]
+[[Category: Zhu J-Y]]
-[[Category: Mitotic chromosome associated protein]]
-[[Category: Protein binding-inhibitor complex]]
-[[Category: Transcription-inhibitor complex]]