6ps9
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of BRD4 bromodomain 1 with N-methylpyrrolidin-2-one (NMP) derivative 17 (5-{2-[(3R)-1-methyl-5-oxopyrrolidin-3-yl]ethyl}-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-1-one)== | |
| + | <StructureSection load='6ps9' size='340' side='right'caption='[[6ps9]], [[Resolution|resolution]] 1.21Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6ps9]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PS9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PS9 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=Y17:5-{2-[(3R)-1-methyl-5-oxopyrrolidin-3-yl]ethyl}-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-1-one'>Y17</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=6ps9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ps9 OCA], [http://pdbe.org/6ps9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ps9 RCSB], [http://www.ebi.ac.uk/pdbsum/6ps9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ps9 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == 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> | ||
| + | == Function == | ||
| + | [[http://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;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | N-Methylpyrrolidone is a solvent molecule which has been shown to compete with acetyl-lysine-containing peptides for binding to bromodomains. From crystallographic studies, it has also been shown to closely mimic the acetamide binding motif in several bromodomains, but has not yet been directly pursued as a fragment in bromodomain inhibition. In this paper, we report the elaboration of N-methylpyrrolidone as a potential lead in fragment-based drug design. Firstly, N-methylpyrrolidone was functionalised to provide points for chemical elaboration. Then, the moiety was incorporated into analogues of the reported bromodomain inhibitor, Olinone. X-ray crystallography revealed that the modified analogues showed comparable binding affinity and structural mimicry to Olinone in the bromodomain binding site. | ||
| - | + | Synthesis and elaboration of N-methylpyrrolidone as an acetamide fragment substitute in bromodomain inhibition.,Hilton-Proctor JP, Ilyichova O, Zheng Z, Jennings IG, Johnstone RW, Shortt J, Mountford SJ, Scanlon MJ, Thompson PE Bioorg Med Chem. 2019 Dec 15;27(24):115157. doi: 10.1016/j.bmc.2019.115157. Epub , 2019 Oct 28. PMID:31727451<ref>PMID:31727451</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6ps9" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Ilyichova, O V]] | ||
| + | [[Category: Scanlon, M J]] | ||
| + | [[Category: Brd4 bd1]] | ||
| + | [[Category: Bromodomain]] | ||
| + | [[Category: Olinone]] | ||
| + | [[Category: Protein binding]] | ||
Revision as of 06:53, 27 November 2019
Crystal structure of BRD4 bromodomain 1 with N-methylpyrrolidin-2-one (NMP) derivative 17 (5-{2-[(3R)-1-methyl-5-oxopyrrolidin-3-yl]ethyl}-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-1-one)
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