5wmd - Revision history

OCA at 14:17, 4 October 2023

2023-10-04T14:17:13Z

←Older revision		Revision as of 14:17, 4 October 2023
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	==N-terminal bromodomain of BRD4 in complex with OTX-015==		==N-terminal bromodomain of BRD4 in complex with OTX-015==
-	<StructureSection load='5wmd' size='340' side='right' caption='[[5wmd]], [[Resolution\|resolution]] 1.27Å' scene=''>	+	<StructureSection load='5wmd' size='340' side='right'caption='[[5wmd]], [[Resolution\|resolution]] 1.27Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5wmd]] 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=5WMD OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5WMD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5wmd]] 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=5WMD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WMD FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6JE:2-[(6S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]-N-(4-hydroxyphenyl)acetamide'>6JE</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]] 1.27Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6JE:2-[(6S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]-N-(4-hydroxyphenyl)acetamide'>6JE</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=5wmd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wmd OCA], [~~http~~://pdbe.org/5wmd PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5wmd RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5wmd PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5wmd ProSAT]</span></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=5wmd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wmd OCA], [https://pdbe.org/5wmd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wmd RCSB], [https://www.ebi.ac.uk/pdbsum/5wmd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wmd ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== 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 ==		== 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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 5wmd" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5wmd" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Bromodomain-containing protein 3D structures\|Bromodomain-containing protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Zhang, Y~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Brd4]]~~	+	[[Category: Zhang Y]]
-	~~[[Category: Bromodomain]]~~	+
-	~~[[Category: Otx-015]]~~	+
-	~~[[Category: Transcription]]~~	+
-	~~[[Category: Transcription-transcription inhibitor complex~~]]	+

OCA at 09:40, 13 February 2019

2019-02-13T09:40:44Z

←Older revision		Revision as of 09:40, 13 February 2019
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	<StructureSection load='5wmd' size='340' side='right' caption='[[5wmd]], [[Resolution\|resolution]] 1.27Å' scene=''>		<StructureSection load='5wmd' size='340' side='right' caption='[[5wmd]], [[Resolution\|resolution]] 1.27Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5wmd]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WMD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WMD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5wmd]] 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=5WMD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WMD FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6JE:2-[(6S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]-N-(4-hydroxyphenyl)acetamide'>6JE</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6JE:2-[(6S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]-N-(4-hydroxyphenyl)acetamide'>6JE</scene></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=5wmd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wmd OCA], [http://pdbe.org/5wmd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wmd RCSB], [http://www.ebi.ac.uk/pdbsum/5wmd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wmd ProSAT]</span></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=5wmd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wmd OCA], [http://pdbe.org/5wmd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wmd RCSB], [http://www.ebi.ac.uk/pdbsum/5wmd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wmd ProSAT]</span></td></tr>
	</table>		</table>
Line 11:		Line 12:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).		[[http://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 (BET) family proteins are key regulators of gene expression in cancer. Herein, we utilize BRD4 profiling to identify critical pathways involved in pathogenesis of chronic lymphocytic leukemia (CLL). BRD4 is overexpressed in CLL and is enriched proximal to genes upregulated or de novo expressed in CLL with known functions in disease pathogenesis and progression. These genes, including key members of the B-cell receptor (BCR) signaling pathway, provide a rationale for this therapeutic approach to identify new targets in alternative types of cancer. Additionally, we describe PLX51107, a structurally distinct BET inhibitor with novel in vitro and in vivo pharmacologic properties that emulates or exceeds the efficacy of BCR signaling agents in preclinical models of CLL. Herein, the discovery of the involvement of BRD4 in the core CLL transcriptional program provides a compelling rationale for clinical investigation of PLX51107 as epigenetic therapy in CLL and application of BRD4 profiling in other cancers.Significance: To date, functional studies of BRD4 in CLL are lacking. Through integrated genomic, functional, and pharmacologic analyses, we uncover the existence of BRD4-regulated core CLL transcriptional programs and present preclinical proof-of-concept studies validating BET inhibition as an epigenetic approach to target BCR signaling in CLL. Cancer Discov; 8(4); 458-77. (c)2018 AACR.This article is highlighted in the In This Issue feature, p. 371.
		+
		+	BRD4 Profiling Identifies Critical Chronic Lymphocytic Leukemia Oncogenic Circuits and Reveals Sensitivity to PLX51107, a Novel Structurally Distinct BET Inhibitor.,Ozer HG, El-Gamal D, Powell B, Hing ZA, Blachly JS, Harrington B, Mitchell S, Grieselhuber NR, Williams K, Lai TH, Alinari L, Baiocchi RA, Brinton L, Baskin E, Cannon M, Beaver L, Goettl VM, Lucas DM, Woyach JA, Sampath D, Lehman AM, Yu L, Zhang J, Ma Y, Zhang Y, Spevak W, Shi S, Severson P, Shellooe R, Carias H, Tsang G, Dong K, Ewing T, Marimuthu A, Tantoy C, Walters J, Sanftner L, Rezaei H, Nespi M, Matusow B, Habets G, Ibrahim P, Zhang C, Mathe EA, Bollag G, Byrd JC, Lapalombella R Cancer Discov. 2018 Apr;8(4):458-477. doi: 10.1158/2159-8290.CD-17-0902. Epub, 2018 Jan 31. PMID:29386193<ref>PMID:29386193</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5wmd" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Zhang, Y]]		[[Category: Zhang, Y]]
	[[Category: Brd4]]		[[Category: Brd4]]

OCA at 18:37, 1 August 2018

2018-08-01T18:37:10Z

←Older revision		Revision as of 18:37, 1 August 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5wmd is ~~ON HOLD until Paper Publication~~	+	==N-terminal bromodomain of BRD4 in complex with OTX-015==
-		+	<StructureSection load='5wmd' size='340' side='right' caption='[[5wmd]], [[Resolution\|resolution]] 1.27Å' scene=''>
-	~~Authors~~: ~~Zhang~~, Y.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5wmd]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WMD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WMD FirstGlance]. <br>
-	~~Description~~: ~~N-terminal bromodomain of~~ BRD4 in ~~complex~~ with ~~OTX~~-~~015~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6JE:2-[(6S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]-N-(4-hydroxyphenyl)acetamide'>6JE</scene></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	<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=5wmd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wmd OCA], [http://pdbe.org/5wmd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wmd RCSB], [http://www.ebi.ac.uk/pdbsum/5wmd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wmd 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>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Zhang, Y]]		[[Category: Zhang, Y]]
		+	[[Category: Brd4]]
		+	[[Category: Bromodomain]]
		+	[[Category: Otx-015]]
		+	[[Category: Transcription]]
		+	[[Category: Transcription-transcription inhibitor complex]]

OCA: Protected "5wmd" [edit=sysop:move=sysop]

2017-09-27T14:58:55Z

Protected "5wmd" [edit=sysop:move=sysop]

←Older revision

Revision as of 14:58, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5wmd is ON HOLD until Paper Publication Authors: Zhang, Y. Description: N-terminal bromodomain of BRD4 in complex with OTX-015 [[Category: Unreleas...

2017-09-27T14:58:54Z

New page: '''Unreleased structure''' The entry 5wmd is ON HOLD until Paper Publication Authors: Zhang, Y. Description: N-terminal bromodomain of BRD4 in complex with OTX-015 [[Category: Unreleas...

New page

'''Unreleased structure'''

The entry 5wmd is ON HOLD until Paper Publication

Authors: Zhang, Y.

Description: N-terminal bromodomain of BRD4 in complex with OTX-015
[[Category: Unreleased Structures]]
[[Category: Zhang, Y]]