7dhs

From Proteopedia

(Difference between revisions)

Current revision

Crystal Structure Analysis of the BRD4

Structural highlights

7dhs 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 1.76Å
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

Bromodomain and extra-terminal proteins (BETs) are potential targets for the therapeutic treatment of prostate cancer (PC). Herein, we report the design, the synthesis, and a structure-activity relationship study of 6-(3,5-dimethylisoxazol-4-yl)benzo[cd]indol-2(1H)-one derivative as novel selective BET inhibitors. One representative compound, 19 (Y06014), bound to BRD4(1) in the low micromolar range and demonstrated high selectivity for BRD4(1) over other non-BET bromodomain-containing proteins. This molecule also potently inhibited cell growth, colony formation, and mRNA expression of AR-regulated genes in PC cell lines. Y06014 also shows stronger activity than the second-generation antiandrogen enzalutamide. Y06014 may serve as a new small molecule probe for further validation of BET as a molecular target for PC drug development.

Y06014 is a selective BET inhibitor for the treatment of prostate cancer.,Wu TB, Xiang QP, Wang C, Wu C, Zhang C, Zhang MF, Liu ZX, Zhang Y, Xiao LJ, Xu Y Acta Pharmacol Sin. 2021 Mar 2. pii: 10.1038/s41401-021-00614-7. doi:, 10.1038/s41401-021-00614-7. PMID:33654218^[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
↑ Wu TB, Xiang QP, Wang C, Wu C, Zhang C, Zhang MF, Liu ZX, Zhang Y, Xiao LJ, Xu Y. Y06014 is a selective BET inhibitor for the treatment of prostate cancer. Acta Pharmacol Sin. 2021 Mar 2. pii: 10.1038/s41401-021-00614-7. doi:, 10.1038/s41401-021-00614-7. PMID:33654218 doi:http://dx.doi.org/10.1038/s41401-021-00614-7

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/7dhs"

@@ Line 1: / Line 1: @@
 ==Crystal Structure Analysis of the BRD4==
-<StructureSection load='7dhs' size='340' side='right'caption='[[7dhs]]' scene=''>
+<StructureSection load='7dhs' size='340' side='right'caption='[[7dhs]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DHS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DHS FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7dhs]] 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=7DHS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DHS FirstGlance]. <br>
-</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=7dhs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dhs OCA], [https://pdbe.org/7dhs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dhs RCSB], [https://www.ebi.ac.uk/pdbsum/7dhs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dhs ProSAT]</span></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]] 1.76&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=H8C:6-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(1R)-1-phenylethyl]benzo[cd]indol-2-one'>H8C</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=7dhs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dhs OCA], [https://pdbe.org/7dhs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dhs RCSB], [https://www.ebi.ac.uk/pdbsum/7dhs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dhs 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 ==
+Bromodomain and extra-terminal proteins (BETs) are potential targets for the therapeutic treatment of prostate cancer (PC). Herein, we report the design, the synthesis, and a structure-activity relationship study of 6-(3,5-dimethylisoxazol-4-yl)benzo[cd]indol-2(1H)-one derivative as novel selective BET inhibitors. One representative compound, 19 (Y06014), bound to BRD4(1) in the low micromolar range and demonstrated high selectivity for BRD4(1) over other non-BET bromodomain-containing proteins. This molecule also potently inhibited cell growth, colony formation, and mRNA expression of AR-regulated genes in PC cell lines. Y06014 also shows stronger activity than the second-generation antiandrogen enzalutamide. Y06014 may serve as a new small molecule probe for further validation of BET as a molecular target for PC drug development.
+Y06014 is a selective BET inhibitor for the treatment of prostate cancer.,Wu TB, Xiang QP, Wang C, Wu C, Zhang C, Zhang MF, Liu ZX, Zhang Y, Xiao LJ, Xu Y Acta Pharmacol Sin. 2021 Mar 2. pii: 10.1038/s41401-021-00614-7. doi:, 10.1038/s41401-021-00614-7. PMID:33654218<ref>PMID:33654218</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 7dhs" 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: Liu Z]]

7dhs

From Proteopedia

Current revision

Crystal Structure Analysis of the BRD4

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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