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| | <StructureSection load='5dw1' size='340' side='right'caption='[[5dw1]], [[Resolution|resolution]] 1.55Å' scene=''> | | <StructureSection load='5dw1' size='340' side='right'caption='[[5dw1]], [[Resolution|resolution]] 1.55Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5dw1]] is a 4 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=5DW1 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5DW1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5dw1]] is a 4 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=5DW1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DW1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5GD:2-{3,5-DIMETHYL-4-[2-(PYRROLIDIN-1-YL)ETHOXY]PHENYL}-5,7-DIMETHOXYQUINAZOLIN-4(3H)-ONE'>5GD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 1.55Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5dw2|5dw2]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5GD:2-{3,5-DIMETHYL-4-[2-(PYRROLIDIN-1-YL)ETHOXY]PHENYL}-5,7-DIMETHOXYQUINAZOLIN-4(3H)-ONE'>5GD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRD2, KIAA9001, RING3 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=5dw1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dw1 OCA], [https://pdbe.org/5dw1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dw1 RCSB], [https://www.ebi.ac.uk/pdbsum/5dw1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dw1 ProSAT]</span></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=5dw1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dw1 OCA], [http://pdbe.org/5dw1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dw1 RCSB], [http://www.ebi.ac.uk/pdbsum/5dw1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dw1 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BRD2_HUMAN BRD2_HUMAN]] May play a role in spermatogenesis or folliculogenesis (By similarity). Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling. Regulates transcription of the CCND1 gene. Plays a role in nucleosome assembly.<ref>PMID:18406326</ref> | + | [https://www.uniprot.org/uniprot/BRD2_HUMAN BRD2_HUMAN] May play a role in spermatogenesis or folliculogenesis (By similarity). Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling. Regulates transcription of the CCND1 gene. Plays a role in nucleosome assembly.<ref>PMID:18406326</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: Fontano, E]] | + | [[Category: Fontano E]] |
| - | [[Category: Suto, R K]] | + | [[Category: Suto RK]] |
| - | [[Category: White, A]] | + | [[Category: White A]] |
| - | [[Category: Bromodomain]]
| + | |
| - | [[Category: Protein binding-inhibitor complex]]
| + | |
| Structural highlights
Function
BRD2_HUMAN May play a role in spermatogenesis or folliculogenesis (By similarity). Binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling. Regulates transcription of the CCND1 gene. Plays a role in nucleosome assembly.[1]
Publication Abstract from PubMed
Bromodomains are epigenetic readers that specifically bind to the acetyl lysine residues of histones and transcription factors. Small molecule BET bromodomain inhibitors can disrupt this interaction which leads to potential modulation of several disease states. Here we describe the binding properties of a novel BET inhibitor RVX-297 that is structurally related to the clinical compound RVX-208, currently undergoing phase III clinical trials for the treatment of cardiovascular diseases, but is distinctly different in its biological and pharmacokinetic profiles. We report that RVX-297 preferentially binds to the BD2 domains of the BET bromodomain and Extra Terminal (BET) family of protein. We demonstrate the differential binding modes of RVX-297 in BD1 and BD2 domains of BRD4 and BRD2 using X-ray crystallography, and describe the structural differences driving the BD2 selective binding of RVX-297. The isothermal titration calorimetry (ITC) data illustrate the related differential thermodynamics of binding of RVX-297 to single as well as dual BET bromodomains.
RVX-297- a novel BD2 selective inhibitor of BET bromodomains.,Kharenko OA, Gesner EM, Patel RG, Norek K, White A, Fontano E, Suto RK, Young PR, McLure KG, Hansen HC Biochem Biophys Res Commun. 2016 Jun 6. pii: S0006-291X(16)30939-1. doi:, 10.1016/j.bbrc.2016.06.021. PMID:27282480[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ LeRoy G, Rickards B, Flint SJ. The double bromodomain proteins Brd2 and Brd3 couple histone acetylation to transcription. Mol Cell. 2008 Apr 11;30(1):51-60. doi: 10.1016/j.molcel.2008.01.018. PMID:18406326 doi:10.1016/j.molcel.2008.01.018
- ↑ Kharenko OA, Gesner EM, Patel RG, Norek K, White A, Fontano E, Suto RK, Young PR, McLure KG, Hansen HC. RVX-297- a novel BD2 selective inhibitor of BET bromodomains. Biochem Biophys Res Commun. 2016 Jun 6. pii: S0006-291X(16)30939-1. doi:, 10.1016/j.bbrc.2016.06.021. PMID:27282480 doi:http://dx.doi.org/10.1016/j.bbrc.2016.06.021
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