6dl2: Difference between revisions

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-'''Unreleased structure'''
-The entry 6dl2 is ON HOLD  until Paper Publication
+==BRD4 bromodomain 1 in complex with HYB157==
+<StructureSection load='6dl2' size='340' side='right'caption='[[6dl2]], [[Resolution|resolution]] 1.47&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6dl2]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DL2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DL2 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GUJ:3-benzyl-2,9-dimethyl-4H,6H-thieno[2,3-e][1,2,4]triazolo[3,4-c][1,4]oxazepine'>GUJ</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6dl2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dl2 OCA], [http://pdbe.org/6dl2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dl2 RCSB], [http://www.ebi.ac.uk/pdbsum/6dl2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dl2 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[[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>
+== Function ==
+[[http://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 ==
+Proteins of the bromodomain and extra-terminal (BET) family are epigenetics "readers" and promising therapeutic targets for cancer and other human diseases. We describe herein a structure-guided design of [1,4]oxazepines as a new class of BET inhibitors and our subsequent design, synthesis, and evaluation of proteolysis-targeting chimeric (PROTAC) small-molecule BET degraders. Our efforts have led to the discovery of extremely potent BET degraders, exemplified by QCA570, which effectively induces degradation of BET proteins and inhibits cell growth in human acute leukemia cell lines even at low picomolar concentrations. QCA570 achieves complete and durable tumor regression in leukemia xenograft models in mice at well-tolerated dose-schedules. QCA570 is the most potent and efficacious BET degrader reported to date.
-Authors:
+Discovery of QCA570 as an Exceptionally Potent and Efficacious Proteolysis Targeting Chimera (PROTAC) Degrader of the Bromodomain and Extra-Terminal (BET) Proteins Capable of Inducing Complete and Durable Tumor Regression.,Qin C, Hu Y, Zhou B, Fernandez-Salas E, Yang CY, Liu L, McEachern D, Przybranowski S, Wang M, Stuckey J, Meagher J, Bai L, Chen Z, Lin M, Yang J, Ziazadeh DN, Xu F, Hu J, Xiang W, Huang L, Li S, Wen B, Sun D, Wang S J Med Chem. 2018 Aug 9;61(15):6685-6704. doi: 10.1021/acs.jmedchem.8b00506. Epub , 2018 Jul 18. PMID:30019901<ref>PMID:30019901</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6dl2" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Meagher, J L]]
+[[Category: Stuckey, J A]]
+[[Category: Bromodomain]]
+[[Category: Transcription]]