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5hm0

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Crystal structure of the first bromodomain of human BRD4 bound to benzoisoxazoloazepine 3

Structural highlights

5hm0 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 1.395Å
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

In recent years, inhibition of the interaction between the bromodomain and extra-terminal domain (BET) family of chromatin adaptors and acetyl-lysine residues on chromatin has emerged as a promising approach to regulate the expression of important disease-relevant genes, including MYC, BCL-2, and NF-kappaB. Here we describe the identification and characterization of a potent and selective benzoisoxazoloazepine BET bromodomain inhibitor that attenuates BET-dependent gene expression in vivo, demonstrates antitumor efficacy in an MV-4-11 mouse xenograft model, and is currently undergoing human clinical trials for hematological malignancies (CPI-0610).

Identification of a Benzoisoxazoloazepine Inhibitor (CPI-0610) of the Bromodomain and Extra-Terminal (BET) Family as a Candidate for Human Clinical Trials.,Albrecht BK, Gehling VS, Hewitt MC, Vaswani RG, Cote A, Leblanc Y, Nasveschuk CG, Bellon S, Bergeron L, Campbell R, Cantone N, Cooper MR, Cummings RT, Jayaram H, Joshi S, Mertz JA, Neiss A, Normant E, O'Meara M, Pardo E, Poy F, Sandy P, Supko J, Sims RJ 3rd, Harmange JC, Taylor AM, Audia JE J Med Chem. 2016 Feb 4. PMID:26815195^[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
↑ Albrecht BK, Gehling VS, Hewitt MC, Vaswani RG, Cote A, Leblanc Y, Nasveschuk CG, Bellon S, Bergeron L, Campbell R, Cantone N, Cooper MR, Cummings RT, Jayaram H, Joshi S, Mertz JA, Neiss A, Normant E, O'Meara M, Pardo E, Poy F, Sandy P, Supko J, Sims RJ 3rd, Harmange JC, Taylor AM, Audia JE. Identification of a Benzoisoxazoloazepine Inhibitor (CPI-0610) of the Bromodomain and Extra-Terminal (BET) Family as a Candidate for Human Clinical Trials. J Med Chem. 2016 Feb 4. PMID:26815195 doi:http://dx.doi.org/10.1021/acs.jmedchem.5b01882

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/5hm0"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the first bromodomain of human BRD4 bound to benzoisoxazoloazepine 3==
-<StructureSection load='5hm0' size='340' side='right' caption='[[5hm0]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
+<StructureSection load='5hm0' size='340' side='right'caption='[[5hm0]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5hm0]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HM0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HM0 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5hm0]] 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=5HM0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HM0 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=62V:6-(4-CHLOROPHENYL)-1-METHYL-4H-[1,2]OXAZOLO[5,4-D][2]BENZAZEPINE'>62V</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]] 1.395&#8491;</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=5hm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hm0 OCA], [http://pdbe.org/5hm0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hm0 RCSB], [http://www.ebi.ac.uk/pdbsum/5hm0 PDBsum]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=62V:6-(4-CHLOROPHENYL)-1-METHYL-4H-[1,2]OXAZOLO[5,4-D][2]BENZAZEPINE'>62V</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=5hm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hm0 OCA], [https://pdbe.org/5hm0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hm0 RCSB], [https://www.ebi.ac.uk/pdbsum/5hm0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hm0 ProSAT]</span></td></tr>
 </table>
 == 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 ==
-[[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 ==
@@ Line 22: / Line 23: @@
 ==See Also==
-*[[Bromodomain-containing protein|Bromodomain-containing protein]]
+*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Bellon, S F]]
+[[Category: Homo sapiens]]
-[[Category: Jayaram, H]]
+[[Category: Large Structures]]
-[[Category: Poy, F]]
+[[Category: Bellon SF]]
-[[Category: Setser, J W]]
+[[Category: Jayaram H]]
-[[Category: Bromodomain]]
+[[Category: Poy F]]
-[[Category: Transcription]]
+[[Category: Setser JW]]

5hm0

From Proteopedia

Current revision

Crystal structure of the first bromodomain of human BRD4 bound to benzoisoxazoloazepine 3

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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