View source for 5dlz


==FIRST DOMAIN OF HUMAN BROMODOMAIN BRD4 IN COMPLEX WITH INHIBITOR 4-[(1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)oxy]-N-({1-[(3-methylphe methyl]piperidin-4-yl}methyl)butanamide==
<StructureSection load='5dlz' size='340' side='right'caption='[[5dlz]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5dlz]] 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=5DLZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DLZ 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]] 1.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5D1:N-{[1-(3-METHYLBENZYL)PIPERIDIN-4-YL]METHYL}-4-[(1-METHYL-2-OXO-1,2-DIHYDROQUINOLIN-4-YL)OXY]BUTANAMIDE'>5D1</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=5dlz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dlz OCA], [https://pdbe.org/5dlz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dlz RCSB], [https://www.ebi.ac.uk/pdbsum/5dlz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dlz 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 ==
Protein-protein interactions (PPIs) represent an enormous source of opportunity for therapeutic intervention. We and others have recently pinpointed key rules that will help in identifying the next generation of innovative drugs to tackle this challenging class of targets within the next decade. We used these rules to design an oriented chemical library corresponding to a set of diverse 'PPI-like' modulators with cores identified as privileged structures in therapeutics. In this work, we purchased the resulting 1664 structurally diverse compounds and evaluated them on a series of representative protein-protein interfaces with distinct "druggability" potential using Homogeneous Time-Resolved Fluorescence (HTRF(R)) technology. For certain PPI classes, analysis of the hit rates revealed up to 100 enrichment factors compared with non-oriented chemical libraries. This observation correlates with the predicted "druggability" of the targets. A specific focus on selectivity profiles, the three-dimensional (3D) molecular modes of action resolved by X-ray crystallography, and the biological activities of identified hits targeting the well-defined "druggable" bromodomains of the bromo and extraterminal (BET) family are presented as a proof-of-concept. Overall, our present study illustrates the potency of machine learning-based oriented chemical libraries to accelerate the identification of hits targeting PPIs. A generalization of this method to a larger set of compounds will accelerate the discovery of original and potent probes for this challenging class of targets.

Protein-protein interaction inhibition (2P2I)-oriented chemical library accelerates hit discovery.,Milhas S, Raux B, Betzi S, Derviaux C, Roche P, Restouin A, Basse MJ, Rebuffet E, Lugari A, Badol M, Kashyap R, Lissitzky JC, Eydoux C, Hamon V, Gourdel ME, Combes S, Zimmermann P, Aurrand-Lions M, Roux T, Rogers C, Muller S, Knapp S, Trinquet E, Collette Y, Guillemot JC, Morelli X ACS Chem Biol. 2016 May 24. PMID:27219844<ref>PMID:27219844</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5dlz" 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: Betzi S]]
[[Category: Morelli X]]
[[Category: Raux B]]
[[Category: Rebuffet E]]