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| | ==Crystal Structure of the first bromodomain of BRD4 in complex with B16== | | ==Crystal Structure of the first bromodomain of BRD4 in complex with B16== |
| - | <StructureSection load='4pci' size='340' side='right' caption='[[4pci]], [[Resolution|resolution]] 1.25Å' scene=''> | + | <StructureSection load='4pci' size='340' side='right'caption='[[4pci]], [[Resolution|resolution]] 1.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4pci]] 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=4PCI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PCI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4pci]] 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=4PCI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PCI FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2NJ:(4S)-1-METHYL-4-PHENYL-1,3,4,5-TETRAHYDRO-2H-1,5-BENZODIAZEPIN-2-ONE'>2NJ</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2NJ:(4S)-1-METHYL-4-PHENYL-1,3,4,5-TETRAHYDRO-2H-1,5-BENZODIAZEPIN-2-ONE'>2NJ</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4pce|4pce]]</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=4pci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pci OCA], [https://pdbe.org/4pci PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pci RCSB], [https://www.ebi.ac.uk/pdbsum/4pci PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pci ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRD4, HUNK1 ([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=4pci FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pci OCA], [http://pdbe.org/4pci PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4pci RCSB], [http://www.ebi.ac.uk/pdbsum/4pci PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4pci ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref> | + | [https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN] Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). | + | [https://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4pci" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4pci" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Caflisch, A]] | + | [[Category: Large Structures]] |
| - | [[Category: Dong, J]] | + | [[Category: Caflisch A]] |
| - | [[Category: Transcription-transcription inhibitor complex]] | + | [[Category: Dong J]] |
| Structural highlights
Disease
BRD4_HUMAN Note=A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.[1] [2]
Function
BRD4_HUMAN Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
Publication Abstract from PubMed
Bromodomains (BRDs) recognize acetyl-lysine modified histone tails mediating epigenetic processes. BRD4, a protein containing two bromodomains, has emerged as an attractive therapeutic target for several types of cancer as well as inflammatory diseases. Using a fragment-based in silico screening approach, we identified two small molecules that bind to the first bromodomain of BRD4 with low-micromolar affinity and favorable ligand efficiency (0.37kcal/mol per non-hydrogen atom), selectively over other families of bromodomains. Notably, the hit rate of the fragment-based in silico approach is about 10% as only 24 putative inhibitors, from an initial library of about 9 million molecules, were tested in vitro.
Discovery of BRD4 bromodomain inhibitors by fragment-based high-throughput docking.,Zhao H, Gartenmann L, Dong J, Spiliotopoulos D, Caflisch A Bioorg Med Chem Lett. 2014 Jun 1;24(11):2493-6. doi: 10.1016/j.bmcl.2014.04.017. , Epub 2014 Apr 13. PMID:24767840[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ French CA, Miyoshi I, Kubonishi I, Grier HE, Perez-Atayde AR, Fletcher JA. BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma. Cancer Res. 2003 Jan 15;63(2):304-7. PMID:12543779
- ↑ French CA, Miyoshi I, Aster JC, Kubonishi I, Kroll TG, Dal Cin P, Vargas SO, Perez-Atayde AR, Fletcher JA. BRD4 bromodomain gene rearrangement in aggressive carcinoma with translocation t(15;19). Am J Pathol. 2001 Dec;159(6):1987-92. PMID:11733348 doi:10.1016/S0002-9440(10)63049-0
- ↑ Zhao H, Gartenmann L, Dong J, Spiliotopoulos D, Caflisch A. Discovery of BRD4 bromodomain inhibitors by fragment-based high-throughput docking. Bioorg Med Chem Lett. 2014 Jun 1;24(11):2493-6. doi: 10.1016/j.bmcl.2014.04.017. , Epub 2014 Apr 13. PMID:24767840 doi:http://dx.doi.org/10.1016/j.bmcl.2014.04.017
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