7b82 - Revision history

OCA at 12:23, 1 February 2024

OCA — Thu, 01 Feb 2024 12:23:16 GMT

←Older revision		Revision as of 12:23, 1 February 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7b82]] 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=7B82 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B82 FirstGlance]. <br>		<table><tr><td colspan='2'>[[7b82]] 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=7B82 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B82 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=T3H:(2~{S})-1-[4-[[(~{E})-~{N},~{N}-dimethylcarbamimidoyl]amino]phenyl]-~{N}-[[2-(3-methyl-1,2,3-triazol-4-yl)-1~{H}-benzimidazol-5-yl]methyl]pyrrolidine-2-carboxamide'>T3H</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]] 1.25Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=T3H:(2~{S})-1-[4-[[(~{E})-~{N},~{N}-dimethylcarbamimidoyl]amino]phenyl]-~{N}-[[2-(3-methyl-1,2,3-triazol-4-yl)-1~{H}-benzimidazol-5-yl]methyl]pyrrolidine-2-carboxamide'>T3H</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=7b82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b82 OCA], [https://pdbe.org/7b82 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b82 RCSB], [https://www.ebi.ac.uk/pdbsum/7b82 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b82 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=7b82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b82 OCA], [https://pdbe.org/7b82 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b82 RCSB], [https://www.ebi.ac.uk/pdbsum/7b82 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b82 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 7b82" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7b82" 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 06:25, 28 September 2022

OCA — Wed, 28 Sep 2022 06:25:10 GMT

←Older revision		Revision as of 06:25, 28 September 2022
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	==BAZ2A bromodomain in complex with triazole compound MS04-TN03==		==BAZ2A bromodomain in complex with triazole compound MS04-TN03==
-	<StructureSection load='7b82' size='340' side='right'caption='[[7b82]]' scene=''>	+	<StructureSection load='7b82' size='340' side='right'caption='[[7b82]], [[Resolution\|resolution]] 1.25Å' 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=7B82 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B82 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7b82]] 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=7B82 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B82 FirstGlance]. <br>
-	</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=7b82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b82 OCA], [https://pdbe.org/7b82 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b82 RCSB], [https://www.ebi.ac.uk/pdbsum/7b82 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b82 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=T3H:(2~{S})-1-[4-[[(~{E})-~{N},~{N}-dimethylcarbamimidoyl]amino]phenyl]-~{N}-[[2-(3-methyl-1,2,3-triazol-4-yl)-1~{H}-benzimidazol-5-yl]methyl]pyrrolidine-2-carboxamide'>T3H</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=7b82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b82 OCA], [https://pdbe.org/7b82 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b82 RCSB], [https://www.ebi.ac.uk/pdbsum/7b82 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b82 ProSAT]</span></td></tr>
	</table>		</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.
		+
		+	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>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7b82" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Caflisch A]]		[[Category: Caflisch A]]

OCA at 16:26, 20 October 2021

OCA — Wed, 20 Oct 2021 16:26:25 GMT

←Older revision		Revision as of 16:26, 20 October 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 7b82 is ~~ON HOLD until Paper Publication~~	+	==BAZ2A bromodomain in complex with triazole compound MS04-TN03==
-		+	<StructureSection load='7b82' size='340' side='right'caption='[[7b82]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7B82 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7B82 FirstGlance]. <br>
-	~~Description~~:	+	</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=7b82 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7b82 OCA], [https://pdbe.org/7b82 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7b82 RCSB], [https://www.ebi.ac.uk/pdbsum/7b82 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7b82 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Caflisch A]]
		+	[[Category: Cazzanelli G]]
		+	[[Category: Dalle Vedove A]]
		+	[[Category: Lolli G]]
		+	[[Category: Sedykh M]]

OCA: Protected "7b82" [edit=sysop:move=sysop]

OCA — Thu, 24 Dec 2020 07:37:35 GMT

Protected "7b82" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:37, 24 December 2020

OCA: New page: '''Unreleased structure''' The entry 7b82 is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

OCA — Thu, 24 Dec 2020 07:37:34 GMT

New page: '''Unreleased structure''' The entry 7b82 is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7b82 is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]