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==Crystal structure of human BRD4(1) in complex with CN750==
==Crystal structure of human BRD4(1) in complex with CN750==
<StructureSection load='6e4a' size='340' side='right' caption='[[6e4a]], [[Resolution|resolution]] 1.26&Aring;' scene=''>
<StructureSection load='6e4a' size='340' side='right'caption='[[6e4a]], [[Resolution|resolution]] 1.26&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6e4a]] is a 2 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=6E4A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E4A FirstGlance]. <br>
<table><tr><td colspan='2'>[[6e4a]] is a 2 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=6E4A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6E4A FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HRY:5-(4-{[(3-chlorophenyl)methyl]amino}-2-{4-[2-(dimethylamino)ethyl]piperazin-1-yl}quinazolin-6-yl)-1-methylpyridin-2(1H)-one'>HRY</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]] 1.26&#8491;</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HRY:5-(4-{[(3-chlorophenyl)methyl]amino}-2-{4-[2-(dimethylamino)ethyl]piperazin-1-yl}quinazolin-6-yl)-1-methylpyridin-2(1H)-one'>HRY</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=6e4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e4a OCA], [http://pdbe.org/6e4a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e4a RCSB], [http://www.ebi.ac.uk/pdbsum/6e4a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e4a 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=6e4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e4a OCA], [https://pdbe.org/6e4a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6e4a RCSB], [https://www.ebi.ac.uk/pdbsum/6e4a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6e4a 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;">
== Publication Abstract from PubMed ==
A new series of quinazoline-based analogs as potent bromodomain-containing protein 4 (BRD4) inhibitors is described. The structure-activity relationships on 2- and 4-position of quinazoline ring, and the substitution at 6-position that mimic the acetylated lysine are discussed. A co-crystallized structure of 48 (CN750) with BRD4 (BD1) including key inhibitor-protein interactions is also highlighted. Together with preliminary rodent pharmacokinetic results, a new lead (65, CN427) is identified which is suitable for further lead optimization.


Discovery and lead identification of quinazoline-based BRD4 inhibitors.,Yang SM, Urban DJ, Yoshioka M, Strovel JW, Fletcher S, Wang AQ, Xu X, Shah P, Hu X, Hall MD, Jadhav A, Maloney DJ Bioorg Med Chem Lett. 2018 Nov 15;28(21):3483-3488. doi:, 10.1016/j.bmcl.2018.08.039. Epub 2018 Aug 31. PMID:30268702<ref>PMID:30268702</ref>
==See Also==
 
*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6e4a" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Fontano, E]]
[[Category: Large Structures]]
[[Category: Lakshminarasimhan, D]]
[[Category: Fontano E]]
[[Category: Suto, R K]]
[[Category: Lakshminarasimhan D]]
[[Category: White, A]]
[[Category: Suto RK]]
[[Category: Protein binding]]
[[Category: White A]]

Latest revision as of 17:39, 13 March 2024

Crystal structure of human BRD4(1) in complex with CN750Crystal structure of human BRD4(1) in complex with CN750

Structural highlights

6e4a is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.26Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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).

See Also

References

  1. ↑ 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
  2. ↑ 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

6e4a, resolution 1.26Å

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