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5wuu

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Revision as of 07:17, 7 October 2020

Complex structure of the first bromodomain of BRD4 with an inhibitor that containing a 2H-chromen-2-one ring

Structural highlights

5wuu is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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).

Publication Abstract from PubMed

As an epigenetic reader, BRD4 regulates the transcription of important downstream genes that are essential for the survival of tumor cells. Small molecular inhibitors targeting the first bromodomain of BRD4 (BRD4-BD1) have showed promising potentials in the therapies of BRD4-related cancers. Through AlphaScreen-based high-throughput screening assay, a novel small molecular inhibitor was identified, and named DCBD-005, which inhibited the binding between BRD4-BD1 and acetylated lysines with an IC50 value of 0.81+/-0.03muM. The compound DCBD-005 effectively inhibited the viability, caused cell cycle arrest, and induced apoptosis in human leukemia MV4-11 cells. Moreover, the crystal structure of compound DCBD-005 with the BRD4-BD1 was determined at 1.72A resolution, which revealed the binding mechanism of the leading compound, and also provided solid basis for further structure-based optimization. These results indicated that this novel BRD4-BD1 inhibitor DCBD-005 is promising to be developed into a drug candidate in the treatment of BRD4-related diseases.

Discovery of novel BRD4 inhibitors by high-throughput screening, crystallography, and cell-based assays.,Sun Z, Zhang H, Chen Z, Xie Y, Jiang H, Chen L, Ding H, Zhang Y, Jiang H, Zheng M, Luo C Bioorg Med Chem Lett. 2017 May 1;27(9):2003-2009. doi:, 10.1016/j.bmcl.2017.03.012. Epub 2017 Mar 9. PMID:28347667^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Sun Z, Zhang H, Chen Z, Xie Y, Jiang H, Chen L, Ding H, Zhang Y, Jiang H, Zheng M, Luo C. Discovery of novel BRD4 inhibitors by high-throughput screening, crystallography, and cell-based assays. Bioorg Med Chem Lett. 2017 May 1;27(9):2003-2009. doi:, 10.1016/j.bmcl.2017.03.012. Epub 2017 Mar 9. PMID:28347667 doi:http://dx.doi.org/10.1016/j.bmcl.2017.03.012

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5wuu"

@@ Line 1: / Line 1: @@
 ==Complex structure of the first bromodomain of BRD4 with an inhibitor that containing a 2H-chromen-2-one ring==
-<StructureSection load='5wuu' size='340' side='right' caption='[[5wuu]], [[Resolution|resolution]] 1.72&Aring;' scene=''>
+<StructureSection load='5wuu' size='340' side='right'caption='[[5wuu]], [[Resolution|resolution]] 1.72&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5wuu]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WUU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WUU FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5wuu]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WUU OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5WUU FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7UU:~{N}-METHYL-~{N}-[3-[(2-OXIDANYLIDENECHROMEN-4-YL)AMINO]PROPYL]THIOPHENE-2-CARBOXAMIDE'>7UU</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7UU:~{N}-METHYL-~{N}-[3-[(2-OXIDANYLIDENECHROMEN-4-YL)AMINO]PROPYL]THIOPHENE-2-CARBOXAMIDE'>7UU</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=5wuu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wuu OCA], [http://pdbe.org/5wuu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wuu RCSB], [http://www.ebi.ac.uk/pdbsum/5wuu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wuu ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5wuu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wuu OCA], [http://pdbe.org/5wuu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wuu RCSB], [http://www.ebi.ac.uk/pdbsum/5wuu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wuu ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 20: / Line 20: @@
 </div>
 <div class="pdbe-citations 5wuu" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Sun, Z Y]]
 [[Category: Zhang, H]]

5wuu

From Proteopedia

Revision as of 07:17, 7 October 2020

Complex structure of the first bromodomain of BRD4 with an inhibitor that containing a 2H-chromen-2-one ring

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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