5n49: Difference between revisions
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==BRPF2 in complex with Compound 7== | |||
<StructureSection load='5n49' size='340' side='right' caption='[[5n49]], [[Resolution|resolution]] 1.94Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5n49]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N49 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5N49 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8LW:2-(1,3,6-TRIMETHYL-2-OXIDANYLIDENE-BENZIMIDAZOL-5-YL)BENZO[DE]ISOQUINOLINE-1,3-DIONE'>8LW</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=5n49 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n49 OCA], [http://pdbe.org/5n49 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5n49 RCSB], [http://www.ebi.ac.uk/pdbsum/5n49 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5n49 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/BRD1_HUMAN BRD1_HUMAN]] Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity.<ref>PMID:16387653</ref> <ref>PMID:21880731</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Bromodomains (BD) are readers of lysine acetylation marks present in numerous proteins associated with chromatin. Here we describe a dual inhibitor of the bromodomain and PHD finger (BRPF) family member BRPF2 and the TATA box binding protein-associated factors TAF1 and TAF1L. These proteins are found in large chromatin complexes and play important roles in transcription regulation. The substituted benzoisoquinolinedione series was identified by high-throughput screening, and subsequent structure-activity relationship optimization allowed generation of low nanomolar BRPF2 BD inhibitors with strong selectivity against BRPF1 and BRPF3 BDs. In addition, a strong inhibition of TAF1/TAF1L BD2 was measured for most derivatives. The best compound of the series was BAY-299, which is a very potent, dual inhibitor with an IC50 of 67 nM for BRPF2 BD, 8 nM for TAF1 BD2, and 106 nM for TAF1L BD2. Importantly, no activity was measured for BRD4 BDs. Furthermore, cellular activity was evidenced using a BRPF2- or TAF1-histone H3.3 or H4 interaction assay. | |||
Benzoisoquinolinediones as Potent and Selective Inhibitors of BRPF2 and TAF1/TAF1L Bromodomains.,Bouche L, Christ CD, Siegel S, Fernandez-Montalvan AE, Holton SJ, Fedorov O, Ter Laak A, Sugawara T, Stockigt D, Tallant C, Bennett J, Monteiro O, Diaz-Saez L, Siejka P, Meier J, Putter V, Weiske J, Muller S, Huber KVM, Hartung IV, Haendler B J Med Chem. 2017 May 1. doi: 10.1021/acs.jmedchem.7b00306. PMID:28402630<ref>PMID:28402630</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 5n49" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bennett, J]] | |||
[[Category: Bouche, L]] | |||
[[Category: Christ, C D]] | |||
[[Category: Fedorov, O]] | |||
[[Category: Fernandez-Montalvan, A E]] | |||
[[Category: Haendler, B]] | |||
[[Category: Hartung, I V]] | |||
[[Category: Holton, S J]] | |||
[[Category: Huber, K V.M]] | |||
[[Category: Laak, A ter]] | |||
[[Category: Meier, J]] | |||
[[Category: Monteiro, O]] | |||
[[Category: Mueller, S]] | |||
[[Category: Puetter, V]] | |||
[[Category: Saez, L D]] | |||
[[Category: Siegel, S]] | |||
[[Category: Siejka, P]] | |||
[[Category: Stoeckigt, D]] | |||
[[Category: Sugawara, T]] | |||
[[Category: Tallant, C]] | |||
[[Category: Weiske, J]] | |||
[[Category: Bromodomain]] | |||
[[Category: Chemical probe]] | |||
[[Category: Transcription]] | |||
