7qwf - Revision history

OCA at 13:23, 1 February 2024

2024-02-01T13:23:26Z

←Older revision		Revision as of 13:23, 1 February 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7qwf]] 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=7QWF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QWF FirstGlance]. <br>		<table><tr><td colspan='2'>[[7qwf]] 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=7QWF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QWF FirstGlance]. <br>
-	</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=FS6:1-[4-ethyl-2-methyl-5-[2-[2-(methylamino)ethyl]-1,3-thiazol-4-yl]-1~{H}-pyrrol-3-yl]ethanone'>FS6</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 2.25Å</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=FS6:1-[4-ethyl-2-methyl-5-[2-[2-(methylamino)ethyl]-1,3-thiazol-4-yl]-1~{H}-pyrrol-3-yl]ethanone'>FS6</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=7qwf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qwf OCA], [https://pdbe.org/7qwf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qwf RCSB], [https://www.ebi.ac.uk/pdbsum/7qwf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qwf 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=7qwf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qwf OCA], [https://pdbe.org/7qwf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qwf RCSB], [https://www.ebi.ac.uk/pdbsum/7qwf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qwf ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/BAZ2A_HUMAN BAZ2A_HUMAN]] Essential component of the NoRC (nucleolar remodeling complex) complex, a complex that mediates silencing of a fraction of rDNA by recruiting histone-modifying enzymes and DNA methyltransferases, leading to heterochromatin formation and transcriptional silencing. In the complex, it plays a central role by being recruited to rDNA and by targeting chromatin modifying enzymes such as HDAC1, leading to repress RNA polymerase I transcription. Recruited to rDNA via its interaction with TTF1 and its ability to recognize and bind histone H4 acetylated on 'Lys-16' (H4K16ac), leading to deacetylation of H4K5ac, H4K8ac, H4K12ac but not H4K16ac. Specifically binds pRNAs, 150-250 nucleotide RNAs that are complementary in sequence to the rDNA promoter; pRNA-binding is required for heterochromatin formation and rDNA silencing (By similarity).	+	[https://www.uniprot.org/uniprot/BAZ2A_HUMAN BAZ2A_HUMAN] Essential component of the NoRC (nucleolar remodeling complex) complex, a complex that mediates silencing of a fraction of rDNA by recruiting histone-modifying enzymes and DNA methyltransferases, leading to heterochromatin formation and transcriptional silencing. In the complex, it plays a central role by being recruited to rDNA and by targeting chromatin modifying enzymes such as HDAC1, leading to repress RNA polymerase I transcription. Recruited to rDNA via its interaction with TTF1 and its ability to recognize and bind histone H4 acetylated on 'Lys-16' (H4K16ac), leading to deacetylation of H4K5ac, H4K8ac, H4K12ac but not H4K16ac. Specifically binds pRNAs, 150-250 nucleotide RNAs that are complementary in sequence to the rDNA promoter; pRNA-binding is required for heterochromatin formation and rDNA silencing (By similarity).
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 7qwf" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7qwf" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Bromodomain adjacent to zinc finger 3D structures\|Bromodomain adjacent to zinc finger 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 06:13, 28 September 2022

2022-09-28T06:13:51Z

←Older revision		Revision as of 06:13, 28 September 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7qwf is ~~ON HOLD until Paper~~ Publication	+	==BAZ2A bromodomain in complex with acetylpyrrole derivative compound 45==
		+	<StructureSection load='7qwf' size='340' side='right'caption='[[7qwf]], [[Resolution\|resolution]] 2.25Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7qwf]] 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=7QWF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QWF FirstGlance]. <br>
		+	</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=FS6:1-[4-ethyl-2-methyl-5-[2-[2-(methylamino)ethyl]-1,3-thiazol-4-yl]-1~{H}-pyrrol-3-yl]ethanone'>FS6</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=7qwf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qwf OCA], [https://pdbe.org/7qwf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qwf RCSB], [https://www.ebi.ac.uk/pdbsum/7qwf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qwf ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/BAZ2A_HUMAN BAZ2A_HUMAN]] Essential component of the NoRC (nucleolar remodeling complex) complex, a complex that mediates silencing of a fraction of rDNA by recruiting histone-modifying enzymes and DNA methyltransferases, leading to heterochromatin formation and transcriptional silencing. In the complex, it plays a central role by being recruited to rDNA and by targeting chromatin modifying enzymes such as HDAC1, leading to repress RNA polymerase I transcription. Recruited to rDNA via its interaction with TTF1 and its ability to recognize and bind histone H4 acetylated on 'Lys-16' (H4K16ac), leading to deacetylation of H4K5ac, H4K8ac, H4K12ac but not H4K16ac. Specifically binds pRNAs, 150-250 nucleotide RNAs that are complementary in sequence to the rDNA promoter; pRNA-binding is required for heterochromatin formation and rDNA silencing (By similarity).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	BAZ2A is an epigenetic regulator affecting transcription of ribosomal RNA. It is overexpressed in aggressive and recurrent prostate cancer, promoting cellular migration. Its bromodomain is characterized by a shallow and difficult-to-drug pocket. Here, we describe a structure-based fragment-growing campaign for the identification of ligands of the BAZ2A bromodomain. By combining docking, competition binding assays, and protein crystallography, we have extensively explored the interactions of the ligands with the rim of the binding pocket, and in particular ionic interactions with the side chain of Glu1820, which is unique to BAZ2A. We present 23 high-resolution crystal structures of the holo BAZ2A bromodomain and analyze common bromodomain/ligand motifs and favorable intraligand interactions. Binding of some of the compounds is enantiospecific, with affinity in the low micromolar range. The most potent ligand has an equilibrium dissociation constant of 7 muM and a good selectivity over the paralog BAZ2B bromodomain.

-	~~Authors:~~ Dalle Vedove, A., Cazzanelli, G., ~~Caflisch~~, A., Lolli, G.	+	Identification of a BAZ2A-Bromodomain Hit Compound by Fragment Growing.,Dalle Vedove A, Cazzanelli G, Batiste L, Marchand JR, Spiliotopoulos D, Corsi J, D'Agostino VG, Caflisch A, Lolli G ACS Med Chem Lett. 2022 Aug 3;13(9):1434-1443. doi:, 10.1021/acsmedchemlett.2c00173. eCollection 2022 Sep 8. PMID:36105334<ref>PMID:36105334</ref>

-	~~Description~~: ~~BAZ2A bromodomain in complex with acetylpyrrole derivative compound 45~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Dalle Vedove,~~ A]]	+	<div class="pdbe-citations 7qwf" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Lolli,~~ G]]	+	== References ==
-	[[Category: ~~Caflisch,~~ A]]	+	<references/>
-	[[Category: ~~Cazzanelli,~~ G]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Caflisch A]]
		+	[[Category: Cazzanelli G]]
		+	[[Category: Dalle Vedove A]]
		+	[[Category: Lolli G]]

OCA at 06:25, 23 February 2022

2022-02-23T06:25:09Z

←Older revision		Revision as of 06:25, 23 February 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7qwf is ON HOLD	+	The entry 7qwf is ON HOLD until Paper Publication

	Authors: Dalle Vedove, A., Cazzanelli, G., Caflisch, A., Lolli, G.		Authors: Dalle Vedove, A., Cazzanelli, G., Caflisch, A., Lolli, G.

OCA: Protected "7qwf" [edit=sysop:move=sysop]

2022-02-02T05:28:49Z

Protected "7qwf" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:28, 2 February 2022

OCA: New page: '''Unreleased structure''' The entry 7qwf is ON HOLD Authors: Dalle Vedove, A., Cazzanelli, G., Caflisch, A., Lolli, G. Description: BAZ2A bromodomain in complex with acetylpyrrole der...

2022-02-02T05:28:48Z

New page: '''Unreleased structure''' The entry 7qwf is ON HOLD Authors: Dalle Vedove, A., Cazzanelli, G., Caflisch, A., Lolli, G. Description: BAZ2A bromodomain in complex with acetylpyrrole der...

New page

'''Unreleased structure'''

The entry 7qwf is ON HOLD

Authors: Dalle Vedove, A., Cazzanelli, G., Caflisch, A., Lolli, G.

Description: BAZ2A bromodomain in complex with acetylpyrrole derivative compound 45
[[Category: Unreleased Structures]]
[[Category: Dalle Vedove, A]]
[[Category: Lolli, G]]
[[Category: Caflisch, A]]
[[Category: Cazzanelli, G]]