View source for 6psb


==Crystal structure of BRD4 bromodomain 1 with N-methylpyrrolidin-2-one (NMP) derivative 18 (5-{[(3R)-1-methyl-5-oxopyrrolidin-3-yl]methyl}-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-1-one)==
<StructureSection load='6psb' size='340' side='right'caption='[[6psb]], [[Resolution|resolution]] 1.59&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6psb]] 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=6PSB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PSB FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.59&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=Y18:5-{[(3R)-1-methyl-5-oxopyrrolidin-3-yl]methyl}-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indol-1-one'>Y18</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=6psb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6psb OCA], [https://pdbe.org/6psb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6psb RCSB], [https://www.ebi.ac.uk/pdbsum/6psb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6psb ProSAT]</span></td></tr>
</table>
== Disease ==
[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 ==
[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;">
== 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6psb" style="background-color:#fffaf0;"></div>

==See Also==
*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ilyichova OV]]
[[Category: Scanlon MJ]]