View source for 5a83


==Crystal structure of human ATAD2 bromodomain in complex with 4-((3R, 4R)-4-3-methyl-5-(5-methylpyridin-3-yl)-2-oxo-1,2-dihydroquinolin-8- yl-aminopiperidin-3-yloxymethyl)-1-thiane-1,1-dione==
<StructureSection load='5a83' size='340' side='right'caption='[[5a83]], [[Resolution|resolution]] 2.09&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5a83]] 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=5A83 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5A83 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]] 2.09&#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=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=YD3:8-[[(3R,4R)-3-[[1,1-BIS(OXIDANYLIDENE)THIAN-4-YL]METHOXY]PIPERIDIN-4-YL]AMINO]-3-METHYL-5-(5-METHYLPYRIDIN-3-YL)-1H-QUINOLIN-2-ONE'>YD3</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=5a83 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5a83 OCA], [https://pdbe.org/5a83 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5a83 RCSB], [https://www.ebi.ac.uk/pdbsum/5a83 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5a83 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ATAD2_HUMAN ATAD2_HUMAN] May be a transcriptional coactivator of the nuclear receptor ESR1 required to induce the expression of a subset of estradiol target genes, such as CCND1, MYC and E2F1. May play a role in the recruitment or occupancy of CREBBP at some ESR1 target gene promoters. May be required for histone hyperacetylation. Involved in the estrogen-induced cell proliferation and cell cycle progression of breast cancer cells.<ref>PMID:17998543</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
ATAD2 is a bromodomain-containing protein whose overexpression is linked to poor outcomes in a number of different cancer types. To date, no potent and selective inhibitors of the bromodomain have been reported. This article describes the structure-based optimization of a series of naphthyridones from micromolar leads with no selectivity over the BET bromodomains to inhibitors with sub-100 nM ATAD2 potency and 100-fold BET selectivity.

Structure-Based Optimization of Naphthyridones into Potent ATAD2 Bromodomain Inhibitors.,Bamborough P, Chung CW, Furze RC, Grandi P, Michon AM, Sheppard RJ, Barnett H, Diallo H, Dixon DP, Douault C, Jones EJ, Karamshi B, Mitchell DJ, Prinjha RK, Rau C, Watson RJ, Werner T, Demont EH J Med Chem. 2015 Jul 31. PMID:26230603<ref>PMID:26230603</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5a83" style="background-color:#fffaf0;"></div>

==See Also==
*[[ATPase family AAA domain-containing protein|ATPase family AAA domain-containing protein]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Bamborough P]]
[[Category: Chung C]]
[[Category: Demont E]]