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| | <StructureSection load='6vuc' size='340' side='right'caption='[[6vuc]], [[Resolution|resolution]] 1.55Å' scene=''> | | <StructureSection load='6vuc' size='340' side='right'caption='[[6vuc]], [[Resolution|resolution]] 1.55Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6vuc]] 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=6VUC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6VUC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6vuc]] 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=6VUC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VUC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RLS:(4R)-1-methyl-4-{4-[(piperidin-1-yl)sulfonyl]phenyl}pyrrolidin-2-one'>RLS</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='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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RLS:(4R)-1-methyl-4-{4-[(piperidin-1-yl)sulfonyl]phenyl}pyrrolidin-2-one'>RLS</scene></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=6vuc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vuc OCA], [http://pdbe.org/6vuc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vuc RCSB], [http://www.ebi.ac.uk/pdbsum/6vuc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vuc 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=6vuc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vuc OCA], [https://pdbe.org/6vuc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vuc RCSB], [https://www.ebi.ac.uk/pdbsum/6vuc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vuc 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 6vuc" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6vuc" 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: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ilyichova, O V]] | + | [[Category: Ilyichova OV]] |
| - | [[Category: Scanlon, M J]] | + | [[Category: Scanlon MJ]] |
| - | [[Category: Thompson, P E]] | + | [[Category: Thompson PE]] |
| - | [[Category: Brd4 bd1]]
| + | |
| - | [[Category: Bromodomain]]
| + | |
| - | [[Category: Nmp]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| 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
N-Methylpyrrolidone is one of several chemotypes that have been described as a mimetic of acetyl-lysine in the development of bromodomain inhibitors. In this paper, we describe the synthesis of a 4-phenyl substituted analogue - 1-methyl-4-phenylpyrrolidin-2-one - and the use of aryl substitution reactions as a divergent route for derivatives. Ultimately, this has led to structurally complex, chiral compounds with progressively improved affinity as inhibitors of bromodomain-containing protein 4.
Substituted 1-methyl-4-phenylpyrrolidin-2-ones - Fragment-based design of N-methylpyrrolidone-derived bromodomain inhibitors.,Hilton-Proctor JP, Ilyichova O, Zheng Z, Jennings IG, Johnstone RW, Shortt J, Mountford SJ, Scanlon MJ, Thompson PE Eur J Med Chem. 2020 Apr 1;191:112120. doi: 10.1016/j.ejmech.2020.112120. Epub, 2020 Feb 12. PMID:32120339[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
- ↑ Hilton-Proctor JP, Ilyichova O, Zheng Z, Jennings IG, Johnstone RW, Shortt J, Mountford SJ, Scanlon MJ, Thompson PE. Substituted 1-methyl-4-phenylpyrrolidin-2-ones - Fragment-based design of N-methylpyrrolidone-derived bromodomain inhibitors. Eur J Med Chem. 2020 Apr 1;191:112120. doi: 10.1016/j.ejmech.2020.112120. Epub, 2020 Feb 12. PMID:32120339 doi:http://dx.doi.org/10.1016/j.ejmech.2020.112120
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