6mh1 - Revision history

OCA at 14:43, 13 March 2024

OCA — Wed, 13 Mar 2024 14:43:00 GMT

←Older revision		Revision as of 14:43, 13 March 2024
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	<StructureSection load='6mh1' size='340' side='right'caption='[[6mh1]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='6mh1' size='340' side='right'caption='[[6mh1]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6mh1]] is a 2 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=6MH1 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6MH1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6mh1]] is a 2 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=6MH1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MH1 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=JQP:N-(3,5-dimethylphenyl)-4-[4-(4-fluorophenyl)-1-(piperidin-4-yl)-1H-imidazol-5-yl]pyrimidin-2-amine'>JQP</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]] 1.6Å</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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=JQP:N-(3,5-dimethylphenyl)-4-[4-(4-fluorophenyl)-1-(piperidin-4-yl)-1H-imidazol-5-yl]pyrimidin-2-amine'>JQP</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=6mh1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mh1 OCA], [~~http~~://pdbe.org/6mh1 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6mh1 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6mh1 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6mh1 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=6mh1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mh1 OCA], [https://pdbe.org/6mh1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mh1 RCSB], [https://www.ebi.ac.uk/pdbsum/6mh1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mh1 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;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	As regulators of transcription, epigenetic proteins that interpret post-translational modifications to N-terminal histone tails are essential for maintaining cellular homeostasis. When dysregulated, "reader" proteins become drivers of disease. In the case of bromodomains, which recognize N-epsilon-acetylated lysine, selective inhibition of individual bromodomain-and-extra-terminal (BET)-family bromodomains has proven challenging. We describe the >55-fold N-terminal-BET bromodomain selectivity of 1,4,5-trisubstituted-imidazole dual kinase-bromodomain inhibitors. Selectivity for the BRD4 N-terminal bromodomain (BRD4(1)) over its second bromodomain (BRD4(2)) arises from the displacement of ordered waters and the conformational flexibility of lysine-141 in BRD4(1). Cellular efficacy was demonstrated via reduction of c-Myc expression, inhibition of NF-kappaB signaling, and suppression of IL-8 production through potential synergistic inhibition of BRD4(1) and p38alpha. These dual inhibitors provide a new scaffold for domain-selective inhibition of BRD4, the aberrant function of which plays a key role in cancer and inflammatory signaling.	+

-	~~Molecular Basis for the N-Terminal~~ Bromodomain-~~and-Extra-Terminal-Family Selectivity of a Dual Kinase-~~Bromodomain Inhibitor.,Divakaran A, Talluri SK, Ayoub AM, Mishra NK, Cui H, Widen JC, Berndt N, Zhu JY, Carlson AS, Topczewski JJ, Schonbrunn EK, Harki DA, Pomerantz WCK J Med Chem. 2018 Oct 25;61(20):9316-9334. doi: 10.1021/acs.jmedchem.8b01248. Epub, 2018 Oct 16. PMID:30253095<ref>PMID:30253095</ref>	+	==See Also==
-		+	*[[Bromodomain-containing protein 3D structures\|Bromodomain-containing protein 3D structures]]
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 6mh1" style="background~~-~~color:#fffaf0;"></div>~~	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Schonbrunn, E]]	+	[[Category: Schonbrunn E]]
-	[[Category: Zhu, J Y]]	+	[[Category: Zhu J-Y]]
-	~~[[Category: Cap]]~~	+
-	~~[[Category: Hunk1]]~~	+
-	~~[[Category: Inflammation]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Map-kinase inhibition]]~~	+
-	~~[[Category: Mcap]]~~	+
-	~~[[Category: Protein binding-inhibitor complex]]~~	+
-	~~[[Category: Transcription-inhibitor complex]]~~	+
-	~~[[Category: Transcription-transcription inhibitor complex~~]]	+

OCA at 08:48, 27 November 2019

OCA — Wed, 27 Nov 2019 08:48:08 GMT

←Older revision		Revision as of 08:48, 27 November 2019
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	<StructureSection load='6mh1' size='340' side='right'caption='[[6mh1]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='6mh1' size='340' side='right'caption='[[6mh1]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6mh1]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MH1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MH1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6mh1]] is a 2 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=6MH1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MH1 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=JQP:N-(3,5-dimethylphenyl)-4-[4-(4-fluorophenyl)-1-(piperidin-4-yl)-1H-imidazol-5-yl]pyrimidin-2-amine'>JQP</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=JQP:N-(3,5-dimethylphenyl)-4-[4-(4-fluorophenyl)-1-(piperidin-4-yl)-1H-imidazol-5-yl]pyrimidin-2-amine'>JQP</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=6mh1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mh1 OCA], [http://pdbe.org/6mh1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mh1 RCSB], [http://www.ebi.ac.uk/pdbsum/6mh1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mh1 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=6mh1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mh1 OCA], [http://pdbe.org/6mh1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mh1 RCSB], [http://www.ebi.ac.uk/pdbsum/6mh1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mh1 ProSAT]</span></td></tr>
	</table>		</table>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Schonbrunn, E]]		[[Category: Schonbrunn, E]]

OCA at 05:53, 7 August 2019

OCA — Wed, 07 Aug 2019 05:53:17 GMT

←Older revision		Revision as of 05:53, 7 August 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6mh1 is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==CRYSTAL STRUCTURE OF THE FIRST BROMODOMAIN OF HUMAN BRD4 IN COMPLEX WITH HU-10, A 1,4,5-Trisubstituted Imidazole Analogue==
		+	<StructureSection load='6mh1' size='340' side='right'caption='[[6mh1]], [[Resolution\|resolution]] 1.60Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6mh1]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MH1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MH1 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=JQP:N-(3,5-dimethylphenyl)-4-[4-(4-fluorophenyl)-1-(piperidin-4-yl)-1H-imidazol-5-yl]pyrimidin-2-amine'>JQP</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=6mh1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mh1 OCA], [http://pdbe.org/6mh1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mh1 RCSB], [http://www.ebi.ac.uk/pdbsum/6mh1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mh1 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 ==
		+	As regulators of transcription, epigenetic proteins that interpret post-translational modifications to N-terminal histone tails are essential for maintaining cellular homeostasis. When dysregulated, "reader" proteins become drivers of disease. In the case of bromodomains, which recognize N-epsilon-acetylated lysine, selective inhibition of individual bromodomain-and-extra-terminal (BET)-family bromodomains has proven challenging. We describe the >55-fold N-terminal-BET bromodomain selectivity of 1,4,5-trisubstituted-imidazole dual kinase-bromodomain inhibitors. Selectivity for the BRD4 N-terminal bromodomain (BRD4(1)) over its second bromodomain (BRD4(2)) arises from the displacement of ordered waters and the conformational flexibility of lysine-141 in BRD4(1). Cellular efficacy was demonstrated via reduction of c-Myc expression, inhibition of NF-kappaB signaling, and suppression of IL-8 production through potential synergistic inhibition of BRD4(1) and p38alpha. These dual inhibitors provide a new scaffold for domain-selective inhibition of BRD4, the aberrant function of which plays a key role in cancer and inflammatory signaling.

-	~~Authors~~:	+	Molecular Basis for the N-Terminal Bromodomain-and-Extra-Terminal-Family Selectivity of a Dual Kinase-Bromodomain Inhibitor.,Divakaran A, Talluri SK, Ayoub AM, Mishra NK, Cui H, Widen JC, Berndt N, Zhu JY, Carlson AS, Topczewski JJ, Schonbrunn EK, Harki DA, Pomerantz WCK J Med Chem. 2018 Oct 25;61(20):9316-9334. doi: 10.1021/acs.jmedchem.8b01248. Epub, 2018 Oct 16. PMID:30253095<ref>PMID:30253095</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6mh1" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Schonbrunn, E]]
		+	[[Category: Zhu, J Y]]
		+	[[Category: Cap]]
		+	[[Category: Hunk1]]
		+	[[Category: Inflammation]]
		+	[[Category: Inhibitor]]
		+	[[Category: Map-kinase inhibition]]
		+	[[Category: Mcap]]
		+	[[Category: Protein binding-inhibitor complex]]
		+	[[Category: Transcription-inhibitor complex]]
		+	[[Category: Transcription-transcription inhibitor complex]]

OCA at 06:27, 10 October 2018

OCA — Wed, 10 Oct 2018 06:27:02 GMT

←Older revision		Revision as of 06:27, 10 October 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6mh1 is ON HOLD	+	The entry 6mh1 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6mh1" [edit=sysop:move=sysop]

OCA — Wed, 26 Sep 2018 06:30:55 GMT

Protected "6mh1" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:30, 26 September 2018

OCA: New page: '''Unreleased structure''' The entry 6mh1 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 26 Sep 2018 06:30:53 GMT

New page: '''Unreleased structure''' The entry 6mh1 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6mh1 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]