4cos
From Proteopedia
(Difference between revisions)
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<StructureSection load='4cos' size='340' side='right' caption='[[4cos]], [[Resolution|resolution]] 1.67Å' scene=''> | <StructureSection load='4cos' size='340' side='right' caption='[[4cos]], [[Resolution|resolution]] 1.67Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[4cos]] is a 1 chain structure | + | <table><tr><td colspan='2'>[[4cos]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4COS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4COS FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4cos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cos OCA], [http://pdbe.org/4cos PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cos RCSB], [http://www.ebi.ac.uk/pdbsum/4cos PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cos ProSAT]</span></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=4cos FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cos OCA], [http://pdbe.org/4cos PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cos RCSB], [http://www.ebi.ac.uk/pdbsum/4cos PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cos ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <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 4cos" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: Human]] | ||
[[Category: Arrowsmith, C H]] | [[Category: Arrowsmith, C H]] | ||
[[Category: Bountra, C]] | [[Category: Bountra, C]] | ||
Revision as of 14:55, 22 December 2016
Crystal structure of the PHD-Bromo-PWWP cassette of human PRKCBP1
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