6kei

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of BRD4 bromodomain 1 (BD1) in complex with 16-methoxy-11-methyl-6-[(pyridin-2-yl)methoxy]-2-oxa-11-azatetracyclo[8.6.1.03,8.013,17]heptadeca-1(16),3,5,7,9,13(17),14-heptaen-12-one

Structural highlights

6kei 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 1.451Å
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

Epigenetic regulation is known to play a key role in progression of anti-cancer therapeutics. Lysine acetylation is an important mechanism in controlling gene expression. There has been increasing interest in bromodomain owing to its ability to modulate transcription of various genes as an epigenetic 'reader.' Herein, we report the design, synthesis, and X-ray studies of novel aristoyagonine (benzo[6,7]oxepino[4,3,2-cd]isoindol-2(1H)-one) derivatives and investigate their inhibitory effect against Brd4 bromodomain. Five compounds 8ab, 8bc, 8bd, 8be, and 8bf have been discovered with high binding affinity over the Brd4 protein. Co-crystal structures of these five inhibitors with human Brd4 bromodomain demonstrated that it has a key binding mode occupying the hydrophobic pocket, which is known to be the acetylated lysine binding site. These novel Brd4 bromodomain inhibitors demonstrated impressive inhibitory activity and mode of action for the treatment of cancer diseases.

Synthesis and Structure-Activity Relationships of Aristoyagonine Derivatives as Brd4 Bromodomain Inhibitors with X-ray Co-Crystal Research.,Yoo M, Park TH, Yoo M, Kim Y, Lee JY, Lee KM, Ryu SE, Lee BI, Jung KY, Park CH Molecules. 2021 Mar 17;26(6). pii: molecules26061686. doi:, 10.3390/molecules26061686. PMID:33802888^[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
↑ Yoo M, Park TH, Yoo M, Kim Y, Lee JY, Lee KM, Ryu SE, Lee BI, Jung KY, Park CH. Synthesis and Structure-Activity Relationships of Aristoyagonine Derivatives as Brd4 Bromodomain Inhibitors with X-ray Co-Crystal Research. Molecules. 2021 Mar 17;26(6). pii: molecules26061686. doi:, 10.3390/molecules26061686. PMID:33802888 doi:http://dx.doi.org/10.3390/molecules26061686

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/6kei"

Categories: Homo sapiens | Large Structures | Lee BI | Park TH

@@ Line 3: / Line 3: @@
 <StructureSection load='6kei' size='340' side='right'caption='[[6kei]], [[Resolution|resolution]] 1.45&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6kei]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KEI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KEI FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6kei]] 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=6KEI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KEI FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D6U:16-methoxy-11-methyl-6-[(pyridin-2-yl)methoxy]-2-oxa-11-azatetracyclo[8.6.1.03,8.013,17]heptadeca-1(16),3,5,7,9,13(17),14-heptaen-12-one'>D6U</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</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]] 1.451&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BRD4, HUNK1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D6U:16-methoxy-11-methyl-6-[(pyridin-2-yl)methoxy]-2-oxa-11-azatetracyclo[8.6.1.03,8.013,17]heptadeca-1(16),3,5,7,9,13(17),14-heptaen-12-one'>D6U</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</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=6kei FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kei OCA], [https://pdbe.org/6kei PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kei RCSB], [https://www.ebi.ac.uk/pdbsum/6kei PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kei 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>
+[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).
+[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 21: / Line 21: @@
 </div>
 <div class="pdbe-citations 6kei" 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: Large Structures]]
-[[Category: Lee, B I]]
+[[Category: Lee BI]]
-[[Category: Park, T H]]
+[[Category: Park TH]]
-[[Category: Brd4]]
-[[Category: Bromodomain 1]]
-[[Category: Transcription]]

6kei

From Proteopedia

Current revision

Crystal structure of BRD4 bromodomain 1 (BD1) in complex with 16-methoxy-11-methyl-6-[(pyridin-2-yl)methoxy]-2-oxa-11-azatetracyclo[8.6.1.03,8.013,17]heptadeca-1(16),3,5,7,9,13(17),14-heptaen-12-one

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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