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4yh4

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Revision as of 08:13, 3 May 2023

Crystal structure of human BRD4(1) in complex with 4-[(5-phenylpyridin-3-yl)carbonyl]-3,4-dihydroquinoxalin-2(1H)-one (compound 19d)

Structural highlights

4yh4 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.
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

Bromodomains are key transcriptional regulators that are thought to be druggable epigenetic targets for cancer, inflammation, diabetes and cardiovascular therapeutics. Of particular importance is the first of two bromodomains in bromodomain containing 4 protein (BRD4(1)). Protein-ligand docking in BRD4(1) was used to purchase a small, focused screening set of compounds possessing a large variety of core structures. Within this set, a small number of weak hits each contained a dihydroquinoxalinone ring system. We purchased other analogs with this ring system and further validated the new hit series and obtained improvement in binding inhibition. Limited exploration by new analog synthesis showed that the binding inhibition in a FRET assay could be improved to the low muM level making this new core a potential hit-to-lead series. Additionally, the predicted geometries of the initial hit and an improved analog were confirmed by X-ray co-crystallography with BRD4(1).

Discovery of a new chemical series of BRD4(1) inhibitors using protein-ligand docking and structure-guided design.,Duffy BC, Liu S, Martin GS, Wang R, Hsia MM, Zhao H, Guo C, Ellis M, Quinn JF, Kharenko OA, Norek K, Gesner EM, Young PR, McLure KG, Wagner GS, Lakshminarasimhan D, White A, Suto RK, Hansen HC, Kitchen DB Bioorg Med Chem Lett. 2015 Jul 15;25(14):2818-23. doi:, 10.1016/j.bmcl.2015.04.107. Epub 2015 May 11. PMID:26022843^[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
↑ Duffy BC, Liu S, Martin GS, Wang R, Hsia MM, Zhao H, Guo C, Ellis M, Quinn JF, Kharenko OA, Norek K, Gesner EM, Young PR, McLure KG, Wagner GS, Lakshminarasimhan D, White A, Suto RK, Hansen HC, Kitchen DB. Discovery of a new chemical series of BRD4(1) inhibitors using protein-ligand docking and structure-guided design. Bioorg Med Chem Lett. 2015 Jul 15;25(14):2818-23. doi:, 10.1016/j.bmcl.2015.04.107. Epub 2015 May 11. PMID:26022843 doi:http://dx.doi.org/10.1016/j.bmcl.2015.04.107

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/4yh4"

Categories: Homo sapiens | Large Structures | Lakshminarasimhan D | Suto RK | White A

@@ Line 1: / Line 1: @@
 ==Crystal structure of human BRD4(1) in complex with 4-[(5-phenylpyridin-3-yl)carbonyl]-3,4-dihydroquinoxalin-2(1H)-one (compound 19d)==
-<StructureSection load='4yh4' size='340' side='right' caption='[[4yh4]], [[Resolution|resolution]] 1.33&Aring;' scene=''>
+<StructureSection load='4yh4' size='340' side='right'caption='[[4yh4]], [[Resolution|resolution]] 1.33&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4yh4]] 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=4YH4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YH4 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4yh4]] 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=4YH4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YH4 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=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=Y81:4-[(5-PHENYLPYRIDIN-3-YL)CARBONYL]-3,4-DIHYDROQUINOXALIN-2(1H)-ONE'>Y81</scene></td></tr>
+</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=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=Y81:4-[(5-PHENYLPYRIDIN-3-YL)CARBONYL]-3,4-DIHYDROQUINOXALIN-2(1H)-ONE'>Y81</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4yh3|4yh3]]</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=4yh4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yh4 OCA], [https://pdbe.org/4yh4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yh4 RCSB], [https://www.ebi.ac.uk/pdbsum/4yh4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yh4 ProSAT]</span></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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4yh4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yh4 OCA], [http://pdbe.org/4yh4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yh4 RCSB], [http://www.ebi.ac.uk/pdbsum/4yh4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yh4 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 20: @@
 </div>
 <div class="pdbe-citations 4yh4" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Lakshminarasimhan, D]]
+[[Category: Large Structures]]
-[[Category: Suto, R K]]
+[[Category: Lakshminarasimhan D]]
-[[Category: White, A]]
+[[Category: Suto RK]]
-[[Category: Protein binding]]
+[[Category: White A]]

4yh4

From Proteopedia

Revision as of 08:13, 3 May 2023

Crystal structure of human BRD4(1) in complex with 4-[(5-phenylpyridin-3-yl)carbonyl]-3,4-dihydroquinoxalin-2(1H)-one (compound 19d)

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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