OCA at 12:45, 16 December 2020

2020-12-16T12:45:29Z

←Older revision		Revision as of 12:45, 16 December 2020
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	==Crystal Structure of BRD4(1) bound to inhibitor BUX4 (13)==		==Crystal Structure of BRD4(1) bound to inhibitor BUX4 (13)==
-	<StructureSection load='6sa3' size='340' side='right'caption='[[6sa3]]' scene=''>	+	<StructureSection load='6sa3' size='340' side='right'caption='[[6sa3]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SA3 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6SA3 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6sa3]] 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=6SA3 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6SA3 FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6sa3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sa3 OCA], [http://pdbe.org/6sa3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6sa3 RCSB], [http://www.ebi.ac.uk/pdbsum/6sa3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6sa3 ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=L2N:~{N}-[2-methoxy-5-(4-methylpiperazin-1-yl)sulfonyl-phenyl]-3-methyl-4-oxidanylidene-5,6,7,8-tetrahydro-2~{H}-cyclohepta[c]pyrrole-1-carboxamide'>L2N</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://proteopedia.org/fgij/fg.htm?mol=6sa3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sa3 OCA], [http://pdbe.org/6sa3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6sa3 RCSB], [http://www.ebi.ac.uk/pdbsum/6sa3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6sa3 ProSAT]</span></td></tr>
	</table>		</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 ==
		+	Various malignant human diseases show disturbed signaling pathways due to increased activity of proteins within the epigenetic machinery. Recently, various novel inhibitors for epigenetic regulation have been introduced which promise a great therapeutic benefit. Inhibitors for the bromo- and extra-terminal domain (BET) family were of particular interest after inhibitors had shown a strong antiproliferative effect. More recently, the focus has increasingly shifted to bromodomains (BDs) outside the BET family. Based on previously developed inhibitors, we have optimized a small series of 4-acyl pyrroles, which we further analyzed by ITC, X-ray crystallography, selectivity studies, the NCI60 cell-panel, and GI50 determinations for several cancer cell lines. The inhibitors address both, BET and BRD7/9 BDs, with very high affinity and show a strong antiproliferative effect on various cancer cell lines that could not be observed for BD family selective inhibitors. Furthermore, a synergistic effect on breast cancer (MCF-7) and melanoma (SK-MEL-5) was proven.
		+
		+	4-Acyl Pyrroles as Dual BET-BRD7/9 Bromodomain Inhibitors Address BETi Insensitive Human Cancer Cell Lines.,Hugle M, Regenass P, Warstat R, Hau M, Schmidtkunz K, Lucas X, Wohlwend D, Einsle O, Jung M, Breit B, Gunther S J Med Chem. 2020 Dec 4. doi: 10.1021/acs.jmedchem.0c00478. PMID:33275431<ref>PMID:33275431</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6sa3" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Huegle M]]	+	[[Category: Huegle, M]]
		+	[[Category: Acetylated]]
		+	[[Category: Brd4]]
		+	[[Category: Bromodomain]]
		+	[[Category: Bux4]]
		+	[[Category: Epigenetic reader protein]]
		+	[[Category: Fragment]]
		+	[[Category: Histone tail]]
		+	[[Category: Inhibitor]]
		+	[[Category: Lysine]]
		+	[[Category: Protein binding-inhibitor complex]]
		+	[[Category: Transcription]]

OCA at 06:35, 9 December 2020

2020-12-09T06:35:25Z

←Older revision		Revision as of 06:35, 9 December 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 6sa3 ~~is ON HOLD until Paper Publication~~	+	==Crystal Structure of BRD4(1) bound to inhibitor BUX4 (13)==
-		+	<StructureSection load='6sa3' size='340' side='right'caption='[[6sa3]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SA3 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6SA3 FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6sa3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sa3 OCA], [http://pdbe.org/6sa3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6sa3 RCSB], [http://www.ebi.ac.uk/pdbsum/6sa3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6sa3 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Huegle M]]

OCA: Protected "6sa3" [edit=sysop:move=sysop]

2019-07-24T04:43:14Z

Protected "6sa3" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:43, 24 July 2019

OCA: New page: '''Unreleased structure''' The entry 6sa3 is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

2019-07-24T04:43:13Z

New page: '''Unreleased structure''' The entry 6sa3 is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6sa3 is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]

6sa3 - Revision history

OCA at 12:45, 16 December 2020

OCA at 06:35, 9 December 2020

OCA: Protected "6sa3" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 6sa3 is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures