4nuc - Revision history

OCA at 17:03, 20 September 2023

OCA — Wed, 20 Sep 2023 17:03:47 GMT

←Older revision		Revision as of 17:03, 20 September 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4nuc]] 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=4NUC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NUC FirstGlance]. <br>		<table><tr><td colspan='2'>[[4nuc]] 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=4NUC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NUC FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=435:4-[(E)-(4-HYDROXY-3,5-DIMETHYLPHENYL)DIAZENYL]-N-(PYRIDIN-2-YL)BENZENESULFONAMIDE'>435</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 1.4Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=435:4-[(E)-(4-HYDROXY-3,5-DIMETHYLPHENYL)DIAZENYL]-N-(PYRIDIN-2-YL)BENZENESULFONAMIDE'>435</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=4nuc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nuc OCA], [https://pdbe.org/4nuc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nuc RCSB], [https://www.ebi.ac.uk/pdbsum/4nuc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nuc 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=4nuc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nuc OCA], [https://pdbe.org/4nuc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nuc RCSB], [https://www.ebi.ac.uk/pdbsum/4nuc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nuc ProSAT]</span></td></tr>
	</table>		</table>

OCA at 08:40, 18 January 2023

OCA — Wed, 18 Jan 2023 08:40:21 GMT

←Older revision		Revision as of 08:40, 18 January 2023
Line 1:		Line 1:

	==Crystal structure of the first bromodomain of human BRD4 in complex with MS435 inhibitor==		==Crystal structure of the first bromodomain of human BRD4 in complex with MS435 inhibitor==
-	<StructureSection load='4nuc' size='340' side='right' caption='[[4nuc]], [[Resolution\|resolution]] 1.40Å' scene=''>	+	<StructureSection load='4nuc' size='340' side='right'caption='[[4nuc]], [[Resolution\|resolution]] 1.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4nuc]] 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=4NUC OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4NUC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4nuc]] 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=4NUC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NUC FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=435:4-[(E)-(4-HYDROXY-3,5-DIMETHYLPHENYL)DIAZENYL]-N-(PYRIDIN-2-YL)BENZENESULFONAMIDE'>435</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=435:4-[(E)-(4-HYDROXY-3,5-DIMETHYLPHENYL)DIAZENYL]-N-(PYRIDIN-2-YL)BENZENESULFONAMIDE'>435</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4nud\|4nud]], [[4nue\|4nue]]</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=4nuc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nuc OCA], [https://pdbe.org/4nuc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nuc RCSB], [https://www.ebi.ac.uk/pdbsum/4nuc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nuc 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=4nuc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nuc OCA], [~~http~~://pdbe.org/4nuc PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4nuc RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4nuc PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4nuc 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 24:		Line 22:

	==See Also==		==See Also==
-	*[[Bromodomain-containing protein\|Bromodomain-containing protein]]	+	*[[Bromodomain-containing protein 3D structures\|Bromodomain-containing protein 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Joshua, J~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Plotnikov, A N~~]]	+	[[Category: Joshua J]]
-	[[Category: ~~Zhou, M M~~]]	+	[[Category: Plotnikov AN]]
-	[[Category: ~~Transcription]]~~	+	[[Category: Zhou M-M]]
-	~~[[Category: Transcription factor~~]]	+

OCA at 16:59, 11 August 2016

OCA — Thu, 11 Aug 2016 16:59:41 GMT

←Older revision		Revision as of 16:59, 11 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of the first bromodomain of human BRD4 in complex with MS435 inhibitor==		==Crystal structure of the first bromodomain of human BRD4 in complex with MS435 inhibitor==
	<StructureSection load='4nuc' size='340' side='right' caption='[[4nuc]], [[Resolution\|resolution]] 1.40Å' scene=''>		<StructureSection load='4nuc' size='340' side='right' caption='[[4nuc]], [[Resolution\|resolution]] 1.40Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4nud\|4nud]], [[4nue\|4nue]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4nud\|4nud]], [[4nue\|4nue]]</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='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=4nuc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nuc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4nuc RCSB], [http://www.ebi.ac.uk/pdbsum/4nuc PDBsum]</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=4nuc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nuc OCA], [http://pdbe.org/4nuc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4nuc RCSB], [http://www.ebi.ac.uk/pdbsum/4nuc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4nuc ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4nuc" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Bromodomain-containing protein\|Bromodomain-containing protein]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 09:21, 5 January 2015

OCA — Mon, 05 Jan 2015 09:21:38 GMT

←Older revision		Revision as of 09:21, 5 January 2015
Line 1:		Line 1:
-	~~{{STRUCTURE_4nuc\| PDB=4nuc \| SCENE= }}~~	+	==Crystal structure of the first bromodomain of human BRD4 in complex with MS435 inhibitor==
-	===Crystal structure of the first bromodomain of human BRD4 in complex with MS435 inhibitor===	+	<StructureSection load='4nuc' size='340' side='right' caption='[[4nuc]], [[Resolution\|resolution]] 1.40Å' scene=''>
-	~~{{ABSTRACT_PUBMED_24144283}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4nuc]] 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=4NUC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NUC FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=435:4-[(E)-(4-HYDROXY-3,5-DIMETHYLPHENYL)DIAZENYL]-N-(PYRIDIN-2-YL)BENZENESULFONAMIDE'>435</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4nud\|4nud]], [[4nue\|4nue]]</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=4nuc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nuc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4nuc RCSB], [http://www.ebi.ac.uk/pdbsum/4nuc PDBsum]</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>		[[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 ==
-	==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 ==
		+	BRD4, characterized by two acetyl-lysine binding bromodomains and an extra-terminal (ET) domain, is a key chromatin organizer that directs gene activation in chromatin through transcription factor recruitment, enhancer assembly, and pause release of the RNA polymerase II complex for transcription elongation. BRD4 has been recently validated as a new epigenetic drug target for cancer and inflammation. Our current knowledge of the functional differences of the two bromodomains of BRD4, however, is limited and is hindered by the lack of selective inhibitors. Here, we report our structure-guided development of diazobenzene-based small-molecule inhibitors for the BRD4 bromodomains that have over 90% sequence identity at the acetyl-lysine binding site. Our lead compound, MS436, through a set of water-mediated interactions, exhibits low nanomolar affinity (estimated Ki of 30-50 nM), with preference for the first bromodomain over the second. We demonstrated that MS436 effectively inhibits BRD4 activity in NF-kappaB-directed production of nitric oxide and proinflammatory cytokine interleukin-6 in murine macrophages. MS436 represents a new class of bromodomain inhibitors and will facilitate further investigation of the biological functions of the two bromodomains of BRD4 in gene expression.

-	~~==About this~~ Structure==	+	Structure-guided design of potent diazobenzene inhibitors for the BET bromodomains.,Zhang G, Plotnikov AN, Rusinova E, Shen T, Morohashi K, Joshua J, Zeng L, Mujtaba S, Ohlmeyer M, Zhou MM J Med Chem. 2013 Nov 27;56(22):9251-64. doi: 10.1021/jm401334s. Epub 2013 Nov 11. PMID:24144283<ref>PMID:24144283</ref>
-	~~[[4nuc]] is a 1 chain structure~~. ~~Full crystallographic information is available from [http~~:~~//oca~~.~~weizmann~~.~~ac.il~~/~~oca-bin/ocashort?id=4NUC OCA]~~.	+

-	==~~Reference~~==	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~<ref group="xtra">PMID:024144283</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	</div>
-	[[Category: Joshua, J.]]	+	== References ==
-	[[Category: Plotnikov, A N.]]	+	<references/>
-	[[Category: Zhou, M M.]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Joshua, J]]
		+	[[Category: Plotnikov, A N]]
		+	[[Category: Zhou, M M]]
	[[Category: Transcription]]		[[Category: Transcription]]
	[[Category: Transcription factor]]		[[Category: Transcription factor]]

OCA at 08:59, 2 April 2014

OCA — Wed, 02 Apr 2014 08:59:26 GMT

←Older revision		Revision as of 08:59, 2 April 2014
Line 1:		Line 1:
-	~~'''Unreleased~~ structure~~'''~~	+	{{STRUCTURE_4nuc\| PDB=4nuc \| SCENE= }}
		+	===Crystal structure of the first bromodomain of human BRD4 in complex with MS435 inhibitor===
		+	{{ABSTRACT_PUBMED_24144283}}

-	~~The entry 4nuc~~ is ~~ON HOLD~~	+	==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>

-	~~Authors~~: ~~Plotnikov, A~~.N.~~, Joshua, J., Zhou, M.-M~~.	+	==Function==
		+	[[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).

-	~~Description: Crystal~~ structure ~~of the first bromodomain of human BRD4 in complex with MS435 inhibitor~~	+	==About this Structure==
		+	[[4nuc]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NUC OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:024144283</ref><references group="xtra"/><references/>
		+	[[Category: Joshua, J.]]
		+	[[Category: Plotnikov, A N.]]
		+	[[Category: Zhou, M M.]]
		+	[[Category: Transcription]]
		+	[[Category: Transcription factor]]

OCA: Protected "4nuc" [edit=sysop:move=sysop]

OCA — Wed, 11 Dec 2013 13:08:38 GMT

Protected "4nuc" [edit=sysop:move=sysop]

←Older revision

Revision as of 13:08, 11 December 2013

OCA: New page: '''Unreleased structure''' The entry 4nuc is ON HOLD Authors: Plotnikov, A.N., Joshua, J., Zhou, M.-M. Description: Crystal structure of the first bromodomain of human BRD4 in complex ...

OCA — Wed, 11 Dec 2013 13:08:37 GMT

New page: '''Unreleased structure''' The entry 4nuc is ON HOLD Authors: Plotnikov, A.N., Joshua, J., Zhou, M.-M. Description: Crystal structure of the first bromodomain of human BRD4 in complex ...

New page

'''Unreleased structure'''

The entry 4nuc is ON HOLD

Authors: Plotnikov, A.N., Joshua, J., Zhou, M.-M.

Description: Crystal structure of the first bromodomain of human BRD4 in complex with MS435 inhibitor