View source for 7wl4


==Crystal Structure of the first bromodomain of human BRD4 in complex with the inhibitor SLP-50==
<StructureSection load='7wl4' size='340' side='right'caption='[[7wl4]], [[Resolution|resolution]] 1.82&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7wl4]] is a 4 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=7WL4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WL4 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]] 1.82&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JFU:~{N}-[2-ethyl-6-(4-methylpiperazin-1-yl)-3-oxidanylidene-2,7-diazatricyclo[6.3.1.0^{4,12}]dodeca-1(12),4,6,8,10-pentaen-9-yl]-2,4-bis(fluoranyl)benzenesulfonamide'>JFU</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=7wl4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wl4 OCA], [https://pdbe.org/7wl4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wl4 RCSB], [https://www.ebi.ac.uk/pdbsum/7wl4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wl4 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 ==
Bromodomain-containing protein 4 (BRD4), which is a member of the bromodomain and extra-terminal domain (BET) family, plays an important role in the regulation of gene expression as the "reader" of epigenetic regulation. BRD4 has become a promising target to treat cancer, because the up-regulation of BRD4 expression is closely associated with the occurrence and development of various cancers. At present, several BRD4 inhibitors are in clinical trials for cancer therapy, but no BRD4 inhibitors are on the market. Here, we designed and synthesized a series of compounds bearing pyrrolo[4,3,2-de]quinolin-2(1H)-one scaffold through structural modification of natural products ammosamide B, which is a natural pyrroloquinoline derivative reported for its potential antitumor activity. All target compounds were evaluated for their BRD4 BD1 inhibition activities via the protein thermal shift assays or AlphaSceen assay. The representative compound 49 showed potent activity (IC50 = 120 nM). The co-crystal of compound 49 with BRD4 BD1 was solved to study the structure activity relationship, which showed that 49 could combine with the acetyl lysine binding site and formed a hydrogen bond with the conserved residue Asn140. The results demonstrate that compound 49 is worthy of further investigation as a promising BRD4 inhibitor.

Design, synthesis, and anticancer evaluation of ammosamide B with pyrroloquinoline derivatives as novel BRD4 inhibitors.,Li W, Zhang C, Zhang HE, Dong R, Liu JY, Wang CM, Wang M, Wang YW, Wang C, Zhang Y, Shi L, Xu Y, Sun LP Bioorg Chem. 2022 Jun 6;127:105917. doi: 10.1016/j.bioorg.2022.105917. PMID:35738217<ref>PMID:35738217</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7wl4" 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: Large Structures]]
[[Category: Li W]]
[[Category: Sun L]]
[[Category: Wang C]]
[[Category: Xu Y]]
[[Category: Zhang C]]
[[Category: Zhang Y]]