4j0s
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| - | {{STRUCTURE_4j0s| PDB=4j0s | SCENE= }} | ||
| - | ===Crystal Structure of the first bromodomain of human BRD4 in complex with a 3,5-dimethylisoxazol ligand=== | ||
| - | {{ABSTRACT_PUBMED_23517011}} | ||
| - | == | + | ==Crystal Structure of the first bromodomain of human BRD4 in complex with a 3,5-dimethylisoxazol ligand== |
| - | [[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN | + | <StructureSection load='4j0s' size='340' side='right'caption='[[4j0s]], [[Resolution|resolution]] 1.84Å' scene=''> |
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4j0s]] 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=4J0S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4J0S 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]] 1.84Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1H3:3-(3,5-DIMETHYL-1,2-OXAZOL-4-YL)-5-[(S)-HYDROXY(PHENYL)METHYL]PHENOL'>1H3</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=4j0s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j0s OCA], [https://pdbe.org/4j0s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4j0s RCSB], [https://www.ebi.ac.uk/pdbsum/4j0s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4j0s 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 == | ||
| + | The bromodomain protein module, which binds to acetylated lysine, is emerging as an important epigenetic therapeutic target. We report the structure-guided optimization of 3,5-dimethylisoxazole derivatives to develop potent inhibitors of the BET (bromodomain and extra terminal domain) bromodomain family with good ligand efficiency. X-ray crystal structures of the most potent compounds reveal key interactions required for high affinity at BRD4(1). Cellular studies demonstrate that the phenol and acetate derivatives of the lead compounds showed strong antiproliferative effects on MV4;11 acute myeloid leukemia cells, as shown for other BET bromodomain inhibitors and genetic BRD4 knockdown, whereas the reported compounds showed no general cytotoxicity in other cancer cell lines tested. | ||
| - | + | Optimization of 3,5-dimethylisoxazole derivatives as potent bromodomain ligands.,Hewings DS, Fedorov O, Filippakopoulos P, Martin S, Picaud S, Tumber A, Wells C, Olcina MM, Freeman K, Gill A, Ritchie AJ, Sheppard DW, Russell AJ, Hammond EM, Knapp S, Brennan PE, Conway SJ J Med Chem. 2013 Apr 25;56(8):3217-27. doi: 10.1021/jm301588r. Epub 2013 Apr 5. PMID:23517011<ref>PMID:23517011</ref> | |
| - | + | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| + | <div class="pdbe-citations 4j0s" style="background-color:#fffaf0;"></div> | ||
| - | == | + | ==See Also== |
| - | + | *[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]] | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Arrowsmith CH]] |
| - | [[Category: | + | [[Category: Bountra C]] |
| - | [[Category: | + | [[Category: Conway SJ]] |
| - | [[Category: Edwards | + | [[Category: Edwards A]] |
| - | [[Category: Felletar | + | [[Category: Felletar I]] |
| - | [[Category: Filippakopoulos | + | [[Category: Filippakopoulos P]] |
| - | [[Category: Hewings | + | [[Category: Hewings DS]] |
| - | [[Category: Knapp | + | [[Category: Knapp S]] |
| - | [[Category: Picaud | + | [[Category: Picaud S]] |
| - | [[Category: Qi | + | [[Category: Qi J]] |
| - | [[Category: | + | [[Category: Von Delft F]] |
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Current revision
Crystal Structure of the first bromodomain of human BRD4 in complex with a 3,5-dimethylisoxazol ligand
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Categories: Homo sapiens | Large Structures | Arrowsmith CH | Bountra C | Conway SJ | Edwards A | Felletar I | Filippakopoulos P | Hewings DS | Knapp S | Picaud S | Qi J | Von Delft F
