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5n49

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Revision as of 11:57, 26 August 2020

BRPF2 in complex with Compound 7

Structural highlights

5n49 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	BRD1, BRL, BRPF2 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[BRD1_HUMAN] Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity.^[1] ^[2]

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Doyon Y, Cayrou C, Ullah M, Landry AJ, Cote V, Selleck W, Lane WS, Tan S, Yang XJ, Cote J. ING tumor suppressor proteins are critical regulators of chromatin acetylation required for genome expression and perpetuation. Mol Cell. 2006 Jan 6;21(1):51-64. PMID:16387653 doi:10.1016/j.molcel.2005.12.007
↑ Qin S, Jin L, Zhang J, Liu L, Ji P, Wu M, Wu J, Shi Y. Recognition of unmodified histone H3 by the first PHD finger of bromodomain-PHD finger protein 2 provides insights into the regulation of histone acetyltransferases monocytic leukemic zinc-finger protein (MOZ) and MOZ-related factor (MORF). J Biol Chem. 2011 Oct 21;286(42):36944-55. doi: 10.1074/jbc.M111.244400. Epub, 2011 Aug 31. PMID:21880731 doi:http://dx.doi.org/10.1074/jbc.M111.244400
↑ 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. Benzoisoquinolinediones as Potent and Selective Inhibitors of BRPF2 and TAF1/TAF1L Bromodomains. J Med Chem. 2017 May 1. doi: 10.1021/acs.jmedchem.7b00306. PMID:28402630 doi:http://dx.doi.org/10.1021/acs.jmedchem.7b00306

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5n49"

@@ Line 1: / Line 1: @@
 ==BRPF2 in complex with Compound 7==
-<StructureSection load='5n49' size='340' side='right' caption='[[5n49]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
+<StructureSection load='5n49' size='340' side='right'caption='[[5n49]], [[Resolution|resolution]] 1.94&Aring;' 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>
+<table><tr><td colspan='2'>[[5n49]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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://proteopedia.org/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>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRD1, BRL, BRPF2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/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 ==
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 5n49" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Bennett, J]]
 [[Category: Bouche, L]]

5n49

From Proteopedia

Revision as of 11:57, 26 August 2020

BRPF2 in complex with Compound 7

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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