4meq: Difference between revisions
New page: '''Unreleased structure''' The entry 4meq is ON HOLD Authors: Filippakopoulos, P., Picaud, S., Felletar, I., Martin, S., Fedorov, O., Vidler, L.R., Brown, N., von Delft, F., Arrowsmith,... |
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The | ==Crystal Structure of the first bromodomain of human BRD4 in complex with a 5-methyl-triazolopyrimidine ligand== | ||
<StructureSection load='4meq' size='340' side='right'caption='[[4meq]], [[Resolution|resolution]] 1.77Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4meq]] 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=4MEQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MEQ 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]] 1.77Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=25O:5-METHYL-7-PHENYL[1,2,4]TRIAZOLO[1,5-A]PYRIMIDIN-2-AMINE'>25O</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=4meq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4meq OCA], [https://pdbe.org/4meq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4meq RCSB], [https://www.ebi.ac.uk/pdbsum/4meq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4meq 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 == | |||
Bromodomains (BRDs) are epigenetic readers that recognize acetylated-lysine (KAc) on proteins and are implicated in a number of diseases. We describe a virtual screening approach to identify BRD inhibitors. Key elements of this approach are the extensive design and use of substructure queries to compile a set of commercially available compounds featuring novel putative KAc mimetics and docking this set for final compound selection. We describe the validation of this approach by applying it to the first BRD of BRD4. The selection and testing of 143 compounds lead to the discovery of six novel hits, including four unprecedented KAc mimetics. We solved the crystal structure of four hits, determined their binding mode, and improved their potency through synthesis and the purchase of derivatives. This work provides a validated virtual screening approach that is applicable to other BRDs and describes novel KAc mimetics that can be further explored to design more potent inhibitors. | |||
Discovery of Novel Small-Molecule Inhibitors of BRD4 Using Structure-Based Virtual Screening.,Vidler LR, Filippakopoulos P, Fedorov O, Picaud S, Martin S, Tomsett M, Woodward H, Brown N, Knapp S, Hoelder S J Med Chem. 2013 Oct 3. PMID:24090311<ref>PMID:24090311</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4meq" 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: Arrowsmith CH]] | |||
[[Category: Bountra C]] | |||
[[Category: Brown N]] | |||
[[Category: Edwards AM]] | |||
[[Category: Fedorov O]] | |||
[[Category: Felletar I]] | |||
[[Category: Filippakopoulos P]] | |||
[[Category: Hoelder S]] | |||
[[Category: Knapp S]] | |||
[[Category: Martin S]] | |||
[[Category: Picaud S]] | |||
[[Category: Vidler LR]] | |||
[[Category: Weigelt J]] | |||
[[Category: Von Delft F]] | |||