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| | <StructureSection load='5n49' size='340' side='right'caption='[[5n49]], [[Resolution|resolution]] 1.94Å' scene=''> | | <StructureSection load='5n49' size='340' side='right'caption='[[5n49]], [[Resolution|resolution]] 1.94Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <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> | + | <table><tr><td colspan='2'>[[5n49]] is a 2 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=5N49 OCA]. For a <b>guided tour on the structure components</b> use [https://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" 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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.94Å</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='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://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> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5n49 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n49 OCA], [https://pdbe.org/5n49 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5n49 RCSB], [https://www.ebi.ac.uk/pdbsum/5n49 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5n49 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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> | + | [https://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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bennett, J]] | + | [[Category: Bennett J]] |
| - | [[Category: Bouche, L]] | + | [[Category: Bouche L]] |
| - | [[Category: Christ, C D]] | + | [[Category: Christ CD]] |
| - | [[Category: Fedorov, O]] | + | [[Category: Fedorov O]] |
| - | [[Category: Fernandez-Montalvan, A E]] | + | [[Category: Fernandez-Montalvan AE]] |
| - | [[Category: Haendler, B]] | + | [[Category: Haendler B]] |
| - | [[Category: Hartung, I V]] | + | [[Category: Hartung IV]] |
| - | [[Category: Holton, S J]] | + | [[Category: Holton SJ]] |
| - | [[Category: Huber, K V.M]] | + | [[Category: Huber KVM]] |
| - | [[Category: Laak, A ter]]
| + | [[Category: Meier J]] |
| - | [[Category: Meier, J]] | + | [[Category: Monteiro O]] |
| - | [[Category: Monteiro, O]] | + | [[Category: Mueller S]] |
| - | [[Category: Mueller, S]] | + | [[Category: Puetter V]] |
| - | [[Category: Puetter, V]] | + | [[Category: Saez LD]] |
| - | [[Category: Saez, L D]] | + | [[Category: Siegel S]] |
| - | [[Category: Siegel, S]] | + | [[Category: Siejka P]] |
| - | [[Category: Siejka, P]] | + | [[Category: Stoeckigt D]] |
| - | [[Category: Stoeckigt, D]] | + | [[Category: Sugawara T]] |
| - | [[Category: Sugawara, T]] | + | [[Category: Tallant C]] |
| - | [[Category: Tallant, C]] | + | [[Category: Weiske J]] |
| - | [[Category: Weiske, J]] | + | [[Category: Ter Laak A]] |
| - | [[Category: Bromodomain]] | + | |
| - | [[Category: Chemical probe]]
| + | |
| - | [[Category: Transcription]]
| + | |
| Structural highlights
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.
See Also
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
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