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| | <StructureSection load='5kj0' size='340' side='right'caption='[[5kj0]], [[Resolution|resolution]] 1.51Å' scene=''> | | <StructureSection load='5kj0' size='340' side='right'caption='[[5kj0]], [[Resolution|resolution]] 1.51Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5kj0]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KJ0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5KJ0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5kj0]] 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=5KJ0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KJ0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6TB:4-[[(7~{R})-8-cyclopentyl-7-ethyl-5-methyl-6-oxidanylidene-7~{H}-pteridin-2-yl]-methyl-amino]-3-methoxy-~{N}-(1-methylpiperidin-4-yl)benzamide'>6TB</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 1.51Å</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=5kj0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kj0 OCA], [http://pdbe.org/5kj0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kj0 RCSB], [http://www.ebi.ac.uk/pdbsum/5kj0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kj0 ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6TB:4-[[(7~{R})-8-cyclopentyl-7-ethyl-5-methyl-6-oxidanylidene-7~{H}-pteridin-2-yl]-methyl-amino]-3-methoxy-~{N}-(1-methylpiperidin-4-yl)benzamide'>6TB</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></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=5kj0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kj0 OCA], [https://pdbe.org/5kj0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kj0 RCSB], [https://www.ebi.ac.uk/pdbsum/5kj0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kj0 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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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ember, S W]] | + | [[Category: Ember SW]] |
| - | [[Category: Schonbrunn, E]] | + | [[Category: Schonbrunn E]] |
| - | [[Category: Zhu, J Y]] | + | [[Category: Zhu J-Y]] |
| - | [[Category: Bromodomain]]
| + | |
| - | [[Category: Cap]]
| + | |
| - | [[Category: Cell cycle]]
| + | |
| - | [[Category: Hunk1]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Mcap]]
| + | |
| - | [[Category: Mitotic chromosome associated protein]]
| + | |
| - | [[Category: Protein binding-inhibitor complex]]
| + | |
| - | [[Category: Transcription-inhibitor complex]]
| + | |
| 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
Evaluating the engagement of a small molecule ligand with a protein target in cells provides useful information for chemical probe optimization and pharmaceutical development. While several techniques exist that can be performed in a low-throughput manner, systematic evaluation of large compound libraries remains a challenge. In-cell engagement measurements are especially useful when evaluating compound classes suspected to target multiple cellular factors. In this study we used a bioluminescent resonant energy transfer assay to assess bromodomain engagement by a compound series containing bromodomain- and kinase-biasing polypharmacophores based on the known dual BRD4 bromodomain/PLK1 kinase inhibitor BI2536. With this assay, we discovered several novel agents with bromodomain-selective specificity profiles and cellular activity. Thus, this platform aids in distinguishing molecules whose cellular activity is difficult to assess due to polypharmacologic effects.
Assessment of Bromodomain Target Engagement by a Series of BI2536 Analogues with Miniaturized BET-BRET.,Koblan LW, Buckley DL, Ott CJ, Fitzgerald ME, Ember SW, Zhu JY, Liu S, Roberts JM, Remillard D, Vittori S, Zhang W, Schonbrunn E, Bradner JE ChemMedChem. 2016 Dec 6;11(23):2575-2581. doi: 10.1002/cmdc.201600502. Epub 2016 , Nov 15. PMID:27862999[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
- ↑ Koblan LW, Buckley DL, Ott CJ, Fitzgerald ME, Ember SW, Zhu JY, Liu S, Roberts JM, Remillard D, Vittori S, Zhang W, Schonbrunn E, Bradner JE. Assessment of Bromodomain Target Engagement by a Series of BI2536 Analogues with Miniaturized BET-BRET. ChemMedChem. 2016 Dec 6;11(23):2575-2581. doi: 10.1002/cmdc.201600502. Epub 2016 , Nov 15. PMID:27862999 doi:http://dx.doi.org/10.1002/cmdc.201600502
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