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==BRD4_BD2-A-35165==
==BRD4_BD2-A-35165==
<StructureSection load='5uf0' size='340' side='right' caption='[[5uf0]], [[Resolution|resolution]] 1.35&Aring;' scene=''>
<StructureSection load='5uf0' size='340' side='right'caption='[[5uf0]], [[Resolution|resolution]] 1.35&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5uf0]] 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=5UF0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UF0 FirstGlance]. <br>
<table><tr><td colspan='2'>[[5uf0]] 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=5UF0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UF0 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=89J:2-methyl-5-(methylamino)-6-phenylpyridazin-3(2H)-one'>89J</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]] 1.35&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5uez|5uez]], [[5uey|5uey]], [[5uex|5uex]], [[5uev|5uev]], [[5uep|5uep]], [[5uet|5uet]], [[5ues|5ues]], [[5uer|5uer]], [[5ueq|5ueq]], [[5ueu|5ueu]], [[5ueo|5ueo]], [[5uew|5uew]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=89J:2-methyl-5-(methylamino)-6-phenylpyridazin-3(2H)-one'>89J</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5uf0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uf0 OCA], [https://pdbe.org/5uf0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uf0 RCSB], [https://www.ebi.ac.uk/pdbsum/5uf0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uf0 ProSAT]</span></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=5uf0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uf0 OCA], [http://pdbe.org/5uf0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uf0 RCSB], [http://www.ebi.ac.uk/pdbsum/5uf0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uf0 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 ==
Members of the BET family of bromodomain containing proteins have been identified as potential targets for blocking proliferation in a variety of cancer cell lines. A two-dimensional NMR fragment screen for binders to the bromodomains of BRD4 identified a phenylpyridazinone fragment with a weak binding affinity (1, Ki = 160 muM). SAR investigation of fragment 1, aided by X-ray structure-based design, enabled the synthesis of potent pyridone and macrocyclic pyridone inhibitors exhibiting single digit nanomolar potency in both biochemical and cell based assays. Advanced analogs in these series exhibited high oral exposures in rodent PK studies and demonstrated significant tumor growth inhibition efficacy in mouse flank xenograft models.


Fragment-Based, Structure-Enabled Discovery of Novel Pyridones and Pyridone Macrocycles as Potent Bromodomain and Extra-Terminal Domain (BET) Family Bromodomain Inhibitors.,Wang L, Pratt JK, Soltwedel T, Sheppard GS, Fidanze SD, Liu D, Hasvold LA, Mantei RA, Holms JH, McClellan WJ, Wendt MD, Wada C, Frey R, Hansen TM, Hubbard R, Park CH, Li L, Magoc TJ, Albert DH, Lin X, Warder SE, Kovar P, Huang X, Wilcox D, Wang R, Rajaraman G, Petros AM, Hutchins CW, Panchal SC, Sun C, Elmore SW, Shen Y, Kati WM, McDaniel KF J Med Chem. 2017 Apr 21. doi: 10.1021/acs.jmedchem.7b00017. PMID:28368119<ref>PMID:28368119</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 5uf0" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Park, C H]]
[[Category: Large Structures]]
[[Category: Helix bundle]]
[[Category: Park CH]]
[[Category: Signaling protein-inhibitor complex]]

Latest revision as of 17:26, 6 March 2024

BRD4_BD2-A-35165BRD4_BD2-A-35165

Structural highlights

5uf0 is a 1 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 1.35Å
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

5uf0, resolution 1.35Å

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