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| | <StructureSection load='4qev' size='340' side='right'caption='[[4qev]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='4qev' size='340' side='right'caption='[[4qev]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4qev]] is a 1 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=4QEV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QEV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4qev]] 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=4QEV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4QEV FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2PE:NONAETHYLENE+GLYCOL'>2PE</scene>, <scene name='pdbligand=31O:METHYL+(2R)-2-[(4S)-6-(4-CHLOROPHENYL)-8-METHOXY-1-METHYL-4H-[1,2,4]TRIAZOLO[4,3-A][1,4]BENZODIAZEPIN-4-YL]PROPANOATE'>31O</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2PE:NONAETHYLENE+GLYCOL'>2PE</scene>, <scene name='pdbligand=31O:METHYL+(2R)-2-[(4S)-6-(4-CHLOROPHENYL)-8-METHOXY-1-METHYL-4H-[1,2,4]TRIAZOLO[4,3-A][1,4]BENZODIAZEPIN-4-YL]PROPANOATE'>31O</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4qep|4qep]]</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=4qev FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qev OCA], [https://pdbe.org/4qev PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4qev RCSB], [https://www.ebi.ac.uk/pdbsum/4qev PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4qev ProSAT]</span></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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4qev FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qev OCA], [http://pdbe.org/4qev PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4qev RCSB], [http://www.ebi.ac.uk/pdbsum/4qev PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4qev 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: Baud, M]] | + | [[Category: Baud M]] |
| - | [[Category: Chirgadze, D Y]] | + | [[Category: Chirgadze DY]] |
| - | [[Category: Ciulli, A]] | + | [[Category: Ciulli A]] |
| - | [[Category: Lin-Shiao, E]] | + | [[Category: Lin-Shiao E]] |
| - | [[Category: Tallant, C]] | + | [[Category: Tallant C]] |
| - | [[Category: Bromodomain-containing protein 2]]
| + | |
| - | [[Category: Kiaa9001]]
| + | |
| - | [[Category: Ring3]]
| + | |
| - | [[Category: Transcription regulation]]
| + | |
| - | [[Category: Transcription-transcription 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
Small molecules are useful tools for probing the biological function and therapeutic potential of individual proteins, but achieving selectivity is challenging when the target protein shares structural domains with other proteins. The Bromo and Extra-Terminal (BET) proteins have attracted interest because of their roles in transcriptional regulation, epigenetics, and cancer. The BET bromodomains (protein interaction modules that bind acetyl-lysine) have been targeted by potent small-molecule inhibitors, but these inhibitors lack selectivity for individual family members. We developed an ethyl derivative of an existing small-molecule inhibitor, I-BET/JQ1, and showed that it binds leucine/alanine mutant bromodomains with nanomolar affinity and achieves up to 540-fold selectivity relative to wild-type bromodomains. Cell culture studies showed that blockade of the first bromodomain alone is sufficient to displace a specific BET protein, Brd4, from chromatin. Expansion of this approach could help identify the individual roles of single BET proteins in human physiology and disease.
Chemical biology. A bump-and-hole approach to engineer controlled selectivity of BET bromodomain chemical probes.,Baud MG, Lin-Shiao E, Cardote T, Tallant C, Pschibul A, Chan KH, Zengerle M, Garcia JR, Kwan TT, Ferguson FM, Ciulli A Science. 2014 Oct 31;346(6209):638-41. doi: 10.1126/science.1249830. Epub 2014, Oct 16. PMID:25323695[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
- ↑ Baud MG, Lin-Shiao E, Cardote T, Tallant C, Pschibul A, Chan KH, Zengerle M, Garcia JR, Kwan TT, Ferguson FM, Ciulli A. Chemical biology. A bump-and-hole approach to engineer controlled selectivity of BET bromodomain chemical probes. Science. 2014 Oct 31;346(6209):638-41. doi: 10.1126/science.1249830. Epub 2014, Oct 16. PMID:25323695 doi:http://dx.doi.org/10.1126/science.1249830
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