5z5u - Revision history

OCA at 08:46, 22 November 2023

2023-11-22T08:46:04Z

←Older revision		Revision as of 08:46, 22 November 2023
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	==The first bromodomain of BRD4 with compound BDF-2254==		==The first bromodomain of BRD4 with compound BDF-2254==
-	<StructureSection load='5z5u' size='340' side='right' caption='[[5z5u]], [[Resolution\|resolution]] 1.63Å' scene=''>	+	<StructureSection load='5z5u' size='340' side='right'caption='[[5z5u]], [[Resolution\|resolution]] 1.63Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5z5u]] 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=5Z5U OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5Z5U FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5z5u]] 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=5Z5U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5Z5U FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=96U:2-amino-4-(1H-imidazol~~-1~~-yl)quinoline-6,8-diol'>96U</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]] 1.631Å</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=96U:2-amino-4-(1H-imidazol-1-yl)quinoline-6,8-diol'>96U</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=5z5u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z5u OCA], [~~http~~://pdbe.org/5z5u PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5z5u RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5z5u PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5z5u 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=5z5u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z5u OCA], [https://pdbe.org/5z5u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5z5u RCSB], [https://www.ebi.ac.uk/pdbsum/5z5u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5z5u 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 ==
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 5z5u" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5z5u" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Bromodomain-containing protein 3D structures\|Bromodomain-containing protein 3D structures]]
		+	*[[Collagenase 3D structures\|Collagenase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Luo, C~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Zhang, H~~]]	+	[[Category: Luo C]]
-	[[Category: ~~Brd4]]~~	+	[[Category: Zhang H]]
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Protein binding]]~~	+
-	~~[[Category: Transcription-inhibitor complex~~]]	+

OCA at 08:17, 6 March 2019

2019-03-06T08:17:34Z

←Older revision		Revision as of 08:17, 6 March 2019
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-	'''Unreleased structure'''

-	The ~~entry~~ 5z5u is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==The first bromodomain of BRD4 with compound BDF-2254==
		+	<StructureSection load='5z5u' size='340' side='right' caption='[[5z5u]], [[Resolution\|resolution]] 1.63Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5z5u]] 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=5Z5U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Z5U FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=96U:2-amino-4-(1H-imidazol-1-yl)quinoline-6,8-diol'>96U</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=5z5u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5z5u OCA], [http://pdbe.org/5z5u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5z5u RCSB], [http://www.ebi.ac.uk/pdbsum/5z5u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5z5u 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).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Small molecular inhibitors targeting BRD4 family proteins are emerging as promising therapies in many types of human malignancies. However, whether BRD4, as well as other BET family members, may serve as therapeutic targets in renal cell carcinoma (RCC) remains unknown. In this study, we found that both BRD2 and BRD4 were over-expressed in RCC tissues, knock-down both of which achieved potent anti-proliferative effects in RCC cells. A novel category of BET inhibitors, originated from an approved drug Nitroxoline, were synthesized and evaluated with biochemical and cellular assays, as well as the method of crystallography. The complex crystal structures of several compounds in this category with the first bromodomain of BRD4 (BRD4-BD1) were solved, revealing the binding mechanism and facilitating further structural optimizations. Among them, compound BDF-1253 showed an approximately four-fold improvement in BRD4 inhibition compared with the prototype Nitroxoline and had good selectivity for BET proteins against other bromodomain proteins or epi-enzymes in biochemical assays. Compound BDF-1253 efficiently suppressed the expression of BET downstream genes, impaired RCC cells viability via inducing cell cycle arrest and apoptosis, and decreased tumor growth in RCC xenografts. In summary, these results suggest that inhibition of BET family members has great therapeutic potentials in the treatment of RCC, and the novel series of BET inhibitors reported here are promising to become RCC drug candidates.

-	~~Authors:~~ Zhang, H., ~~Luo~~, C.	+	Development and evaluation of a novel series of Nitroxoline-derived BET inhibitors with antitumor activity in renal cell carcinoma.,Chen W, Zhang H, Chen Z, Jiang H, Liao L, Fan S, Xing J, Xie Y, Chen S, Ding H, Chen K, Jiang H, Luo C, Zheng M, Yao Z, Huang Y, Zhang Y Oncogenesis. 2018 Nov 2;7(11):83. doi: 10.1038/s41389-018-0093-z. PMID:30385738<ref>PMID:30385738</ref>

-	~~Description: The first bromodomain~~ of ~~BRD4 with compound BDF-2254~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	[[Category: ~~Zhang, H~~]]	+	<div class="pdbe-citations 5z5u" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
	[[Category: Luo, C]]		[[Category: Luo, C]]
		+	[[Category: Zhang, H]]
		+	[[Category: Brd4]]
		+	[[Category: Complex]]
		+	[[Category: Inhibitor]]
		+	[[Category: Protein binding]]
		+	[[Category: Transcription-inhibitor complex]]

OCA at 12:14, 11 April 2018

2018-04-11T12:14:23Z

←Older revision		Revision as of 12:14, 11 April 2018
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5z5u is ON HOLD	+	The entry 5z5u is ON HOLD until Paper Publication

	Authors: Zhang, H., Luo, C.		Authors: Zhang, H., Luo, C.

OCA: Protected "5z5u" [edit=sysop:move=sysop]

2018-01-31T04:39:46Z

Protected "5z5u" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:39, 31 January 2018

OCA: New page: '''Unreleased structure''' The entry 5z5u is ON HOLD Authors: Zhang, H., Luo, C. Description: The first bromodomain of BRD4 with compound BDF-2254 Category: Unreleased Structures [...

2018-01-31T04:39:45Z

New page: '''Unreleased structure''' The entry 5z5u is ON HOLD Authors: Zhang, H., Luo, C. Description: The first bromodomain of BRD4 with compound BDF-2254 Category: Unreleased Structures [...

New page

'''Unreleased structure'''

The entry 5z5u is ON HOLD

Authors: Zhang, H., Luo, C.

Description: The first bromodomain of BRD4 with compound BDF-2254
[[Category: Unreleased Structures]]
[[Category: Zhang, H]]
[[Category: Luo, C]]