6hm0 - Revision history

OCA at 11:32, 24 January 2024

2024-01-24T11:32:47Z

←Older revision		Revision as of 11:32, 24 January 2024
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	<StructureSection load='6hm0' size='340' side='right'caption='[[6hm0]], [[Resolution\|resolution]] 2.40Å' scene=''>		<StructureSection load='6hm0' size='340' side='right'caption='[[6hm0]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6hm0]] 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=6HM0 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6HM0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6hm0]] 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=6HM0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HM0 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GBW:(2~{S},4~{S})-1-[(2~{S})-2-[2-[2-[2-[4-[[2,6-dimethoxy-4-(2-methyl-1-oxidanylidene-2,7-naphthyridin-4-yl)phenyl]methyl]piperazin-1-yl]ethoxy]ethoxy]ethanoylamino]-3,3-dimethyl-butanoyl]-~{N}-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-4-oxidanyl-pyrrolidine-2-carboxamide'>GBW</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]] 2.4Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BRD9, UNQ3040/PRO9856 ([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=GBW:(2~{S},4~{S})-1-[(2~{S})-2-[2-[2-[2-[4-[[2,6-dimethoxy-4-(2-methyl-1-oxidanylidene-2,7-naphthyridin-4-yl)phenyl]methyl]piperazin-1-yl]ethoxy]ethoxy]ethanoylamino]-3,3-dimethyl-butanoyl]-~{N}-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-4-oxidanyl-pyrrolidine-2-carboxamide'>GBW</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=6hm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hm0 OCA], [~~http~~://pdbe.org/6hm0 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6hm0 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6hm0 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6hm0 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=6hm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hm0 OCA], [https://pdbe.org/6hm0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hm0 RCSB], [https://www.ebi.ac.uk/pdbsum/6hm0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hm0 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/BRD9_HUMAN BRD9_HUMAN]] May play a role in chromatin remodeling and regulation of transcription.	+	[https://www.uniprot.org/uniprot/BRD9_HUMAN BRD9_HUMAN] May play a role in chromatin remodeling and regulation of transcription.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Ciulli, A]]	+	[[Category: Ciulli A]]
-	[[Category: Hughes~~, S J~~]]	+	[[Category: Hughes SJ]]
-	[[Category: Zoppi, V]]	+	[[Category: Zoppi V]]
-	~~[[Category: Chromatin regulator]]~~	+
-	~~[[Category: Lysine-acetylated histone binding]]~~	+
-	~~[[Category: Protac]]~~	+
-	~~[[Category: Transcription~~]]	+

OCA at 07:57, 24 April 2019

2019-04-24T07:57:38Z

←Older revision		Revision as of 07:57, 24 April 2019
Line 1:		Line 1:

	==Crystal structure of human BRD9 bromodomain in complex with a PROTAC==		==Crystal structure of human BRD9 bromodomain in complex with a PROTAC==
-	<StructureSection load='6hm0' size='340' side='right' caption='[[6hm0]], [[Resolution\|resolution]] 2.40Å' scene=''>	+	<StructureSection load='6hm0' size='340' side='right'caption='[[6hm0]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6hm0]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HM0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HM0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6hm0]] 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=6HM0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HM0 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GBW:(2~{S},4~{S})-1-[(2~{S})-2-[2-[2-[2-[4-[[2,6-dimethoxy-4-(2-methyl-1-oxidanylidene-2,7-naphthyridin-4-yl)phenyl]methyl]piperazin-1-yl]ethoxy]ethoxy]ethanoylamino]-3,3-dimethyl-butanoyl]-~{N}-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-4-oxidanyl-pyrrolidine-2-carboxamide'>GBW</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GBW:(2~{S},4~{S})-1-[(2~{S})-2-[2-[2-[2-[4-[[2,6-dimethoxy-4-(2-methyl-1-oxidanylidene-2,7-naphthyridin-4-yl)phenyl]methyl]piperazin-1-yl]ethoxy]ethoxy]ethanoylamino]-3,3-dimethyl-butanoyl]-~{N}-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-4-oxidanyl-pyrrolidine-2-carboxamide'>GBW</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BRD9, UNQ3040/PRO9856 ([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=6hm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hm0 OCA], [http://pdbe.org/6hm0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hm0 RCSB], [http://www.ebi.ac.uk/pdbsum/6hm0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hm0 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=6hm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hm0 OCA], [http://pdbe.org/6hm0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hm0 RCSB], [http://www.ebi.ac.uk/pdbsum/6hm0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hm0 ProSAT]</span></td></tr>
	</table>		</table>
Line 18:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 6hm0" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6hm0" 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: Large Structures]]
	[[Category: Ciulli, A]]		[[Category: Ciulli, A]]
	[[Category: Hughes, S J]]		[[Category: Hughes, S J]]

OCA at 12:09, 16 January 2019

2019-01-16T12:09:41Z

←Older revision		Revision as of 12:09, 16 January 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6hm0 is ~~ON HOLD~~	+	==Crystal structure of human BRD9 bromodomain in complex with a PROTAC==
		+	<StructureSection load='6hm0' size='340' side='right' caption='[[6hm0]], [[Resolution\|resolution]] 2.40Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6hm0]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HM0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HM0 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GBW:(2~{S},4~{S})-1-[(2~{S})-2-[2-[2-[2-[4-[[2,6-dimethoxy-4-(2-methyl-1-oxidanylidene-2,7-naphthyridin-4-yl)phenyl]methyl]piperazin-1-yl]ethoxy]ethoxy]ethanoylamino]-3,3-dimethyl-butanoyl]-~{N}-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]-4-oxidanyl-pyrrolidine-2-carboxamide'>GBW</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=6hm0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hm0 OCA], [http://pdbe.org/6hm0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hm0 RCSB], [http://www.ebi.ac.uk/pdbsum/6hm0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hm0 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/BRD9_HUMAN BRD9_HUMAN]] May play a role in chromatin remodeling and regulation of transcription.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Developing PROTACs to redirect the ubiquitination activity of E3 ligases and potently degrade a target protein within cells can be a lengthy and unpredictable process, and it remains unclear whether any combination of E3 and target might be productive for degradation. We describe a probe-quality degrader for a ligase-target pair deemed unsuitable: the von Hippel-Lindau (VHL) and BRD9, a bromodomain-containing subunit of the SWI/SNF chromatin remodeling complex BAF. VHL-based degraders could be optimized from suboptimal compounds in two rounds by systematically varying conjugation patterns and linkers, and monitoring cellular degradation activities, kinetic profiles, and ubiquitination, as well as ternary complex formation thermodynamics. The emerged structure-activity relationships guided the discovery of VZ185, a potent, fast and selective degrader of BRD9 and of its close homolog BRD7. Our findings qualify a new chemical tool for BRD7/9 knockdown, and provide a roadmap for PROTAC development against seemingly incompatible target-ligase combinations.

-	~~Authors~~:	+	Iterative design and optimization of initially inactive Proteolysis Targeting Chimeras (PROTACs) identify VZ185 as a potent, fast and selective von Hippel-Lindau (VHL)-based dual degrader probe of BRD9 and BRD7.,Zoppi V, Hughes SJ, Maniaci C, Testa A, Gmaschitz T, Wieshofer C, Koegl M, Riching K, Daniels DL, Spallarossa A, Ciulli A J Med Chem. 2018 Dec 12. doi: 10.1021/acs.jmedchem.8b01413. PMID:30540463<ref>PMID:30540463</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 6hm0" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Ciulli, A]]
		+	[[Category: Hughes, S J]]
		+	[[Category: Zoppi, V]]
		+	[[Category: Chromatin regulator]]
		+	[[Category: Lysine-acetylated histone binding]]
		+	[[Category: Protac]]
		+	[[Category: Transcription]]

OCA: Protected "6hm0" [edit=sysop:move=sysop]

2018-09-19T18:12:32Z

Protected "6hm0" [edit=sysop:move=sysop]

←Older revision

Revision as of 18:12, 19 September 2018

OCA: New page: '''Unreleased structure''' The entry 6hm0 is ON HOLD Authors: Description: Category: Unreleased Structures

2018-09-19T18:12:31Z

New page: '''Unreleased structure''' The entry 6hm0 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6hm0 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]