6qch - Revision history

OCA at 11:57, 24 January 2024

OCA — Wed, 24 Jan 2024 11:57:45 GMT

←Older revision		Revision as of 11:57, 24 January 2024
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	<StructureSection load='6qch' size='340' side='right'caption='[[6qch]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='6qch' size='340' side='right'caption='[[6qch]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6qch]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QCH OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6QCH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6qch]] 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=6QCH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QCH FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AR6:[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL+[HYDROXY-[[(2R,3S,4R,5S)-3,4,5-TRIHYDROXYOXOLAN-2-YL]METHOXY]PHOSPHORYL]+HYDROGEN+PHOSPHATE'>AR6</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HWB:cyanidin'>HWB</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.1Å</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=6qch FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qch OCA], [~~http~~://pdbe.org/6qch PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6qch RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6qch PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6qch ProSAT]</span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AR6:[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL+[HYDROXY-[[(2R,3S,4R,5S)-3,4,5-TRIHYDROXYOXOLAN-2-YL]METHOXY]PHOSPHORYL]+HYDROGEN+PHOSPHATE'>AR6</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HWB:cyanidin'>HWB</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6qch FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qch OCA], [https://pdbe.org/6qch PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qch RCSB], [https://www.ebi.ac.uk/pdbsum/6qch PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qch ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/SIR6_HUMAN SIR6_HUMAN]] NAD-dependent protein deacetylase. Has deacetylase activity towards histone H3K9Ac and H3K56Ac. Modulates acetylation of histone H3 in telomeric chromatin during the S-phase of the cell cycle. Deacetylates histone H3K9Ac at NF-kappa-B target promoters and may down-regulate the expression of a subset of NF-kappa-B target genes. Acts as a corepressor of the transcription factor HIF1A to control the expression of multiple glycolytic genes to regulate glucose homeostasis. Required for genomic stability. Regulates the production of TNF protein. Has a role in the regulation of life span (By similarity). Deacetylation of nucleosomes interferes with RELA binding to target DNA. May be required for the association of WRN with telomeres during S-phase and for normal telomere maintenance. Required for genomic stability. Required for normal IGF1 serum levels and normal glucose homeostasis. Modulates cellular senescence and apoptosis. On DNA damage, promotes DNA end resection via deacetylation of RBBP8. Has very weak deacetylase activity and can bind NAD(+) in the absence of acetylated substrate.<ref>PMID:18337721</ref> <ref>PMID:19135889</ref> <ref>PMID:19625767</ref> <ref>PMID:20829486</ref> <ref>PMID:21362626</ref>	+	[https://www.uniprot.org/uniprot/SIR6_HUMAN SIR6_HUMAN] NAD-dependent protein deacetylase. Has deacetylase activity towards histone H3K9Ac and H3K56Ac. Modulates acetylation of histone H3 in telomeric chromatin during the S-phase of the cell cycle. Deacetylates histone H3K9Ac at NF-kappa-B target promoters and may down-regulate the expression of a subset of NF-kappa-B target genes. Acts as a corepressor of the transcription factor HIF1A to control the expression of multiple glycolytic genes to regulate glucose homeostasis. Required for genomic stability. Regulates the production of TNF protein. Has a role in the regulation of life span (By similarity). Deacetylation of nucleosomes interferes with RELA binding to target DNA. May be required for the association of WRN with telomeres during S-phase and for normal telomere maintenance. Required for genomic stability. Required for normal IGF1 serum levels and normal glucose homeostasis. Modulates cellular senescence and apoptosis. On DNA damage, promotes DNA end resection via deacetylation of RBBP8. Has very weak deacetylase activity and can bind NAD(+) in the absence of acetylated substrate.<ref>PMID:18337721</ref> <ref>PMID:19135889</ref> <ref>PMID:19625767</ref> <ref>PMID:20829486</ref> <ref>PMID:21362626</ref>
	<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 6qch" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6qch" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Histone deacetylase 3D structures\|Histone deacetylase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Steegborn, C]]	+	[[Category: Steegborn C]]
-	[[Category: You, W]]	+	[[Category: You W]]
-	~~[[Category: Activator]]~~	+
-	~~[[Category: Allosteric]]~~	+
-	~~[[Category: Deacylase]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Quercetin derivative~~]]	+

OCA at 09:14, 25 December 2019

OCA — Wed, 25 Dec 2019 09:14:20 GMT

←Older revision		Revision as of 09:14, 25 December 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6qch is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Human Sirt6 in complex with ADP-ribose and the activator cyanidin==
		+	<StructureSection load='6qch' size='340' side='right'caption='[[6qch]], [[Resolution\|resolution]] 2.10Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6qch]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QCH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QCH FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AR6:[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL+[HYDROXY-[[(2R,3S,4R,5S)-3,4,5-TRIHYDROXYOXOLAN-2-YL]METHOXY]PHOSPHORYL]+HYDROGEN+PHOSPHATE'>AR6</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HWB:cyanidin'>HWB</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6qch FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qch OCA], [http://pdbe.org/6qch PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qch RCSB], [http://www.ebi.ac.uk/pdbsum/6qch PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qch ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/SIR6_HUMAN SIR6_HUMAN]] NAD-dependent protein deacetylase. Has deacetylase activity towards histone H3K9Ac and H3K56Ac. Modulates acetylation of histone H3 in telomeric chromatin during the S-phase of the cell cycle. Deacetylates histone H3K9Ac at NF-kappa-B target promoters and may down-regulate the expression of a subset of NF-kappa-B target genes. Acts as a corepressor of the transcription factor HIF1A to control the expression of multiple glycolytic genes to regulate glucose homeostasis. Required for genomic stability. Regulates the production of TNF protein. Has a role in the regulation of life span (By similarity). Deacetylation of nucleosomes interferes with RELA binding to target DNA. May be required for the association of WRN with telomeres during S-phase and for normal telomere maintenance. Required for genomic stability. Required for normal IGF1 serum levels and normal glucose homeostasis. Modulates cellular senescence and apoptosis. On DNA damage, promotes DNA end resection via deacetylation of RBBP8. Has very weak deacetylase activity and can bind NAD(+) in the absence of acetylated substrate.<ref>PMID:18337721</ref> <ref>PMID:19135889</ref> <ref>PMID:19625767</ref> <ref>PMID:20829486</ref> <ref>PMID:21362626</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Mammalian Sirtuin 6 (Sirt6) is an NAD(+)-dependent protein deacylase regulating metabolism and chromatin homeostasis. Sirt6 activation protects against metabolic and aging-related diseases, and Sirt6 inhibition is considered a cancer therapy. Available Sirt6 modulators show insufficient potency and specificity, and even partially contradictory Sirt6 effects were reported for the plant flavone quercetin. To understand Sirt6 modulation by quercetin-based compounds, we analysed their binding and activity effects on Sirt6 and other Sirtuin isoforms and solved crystal structures of compound complexes with Sirt6 and Sirt2. We find that quercetin activates Sirt6 via the isoform-specific binding site for pyrrolo[1,2-a]quinoxalines. Its inhibitory effect on other isoforms is based on an alternative binding site at the active site entrance. Based on these insights, we identified isoquercetin as a ligand that can discriminate both sites and thus activates Sirt6 with increased specificity. Furthermore, we find that quercetin derivatives that inhibit rather than activate Sirt6 exploit the same general Sirt6 binding site as the activators, identifying it as a versatile allosteric site for Sirt6 modulation. Our results thus provide a structural basis for Sirtuin effects of quercetin-related compounds and helpful insights for Sirt6-targeted drug development.

-	~~Authors:~~ You, W., ~~Steegborn~~, C.	+	Structural basis for the activation and inhibition of Sirtuin 6 by quercetin and its derivatives.,You W, Zheng W, Weiss S, Chua KF, Steegborn C Sci Rep. 2019 Dec 16;9(1):19176. doi: 10.1038/s41598-019-55654-1. PMID:31844103<ref>PMID:31844103</ref>

-	~~Description: Human Sirt6 in complex with ADP-ribose and~~ the ~~activator cyanidin~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	[[Category: ~~You, W~~]]	+	<div class="pdbe-citations 6qch" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Steegborn, C]]		[[Category: Steegborn, C]]
		+	[[Category: You, W]]
		+	[[Category: Activator]]
		+	[[Category: Allosteric]]
		+	[[Category: Deacylase]]
		+	[[Category: Hydrolase]]
		+	[[Category: Quercetin derivative]]

OCA at 06:52, 30 January 2019

OCA — Wed, 30 Jan 2019 06:52:23 GMT

←Older revision		Revision as of 06:52, 30 January 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: You, W., Steegborn, C.		Authors: You, W., Steegborn, C.

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

OCA — Wed, 09 Jan 2019 05:08:52 GMT

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

←Older revision

Revision as of 05:08, 9 January 2019

OCA: New page: '''Unreleased structure''' The entry 6qch is ON HOLD Authors: You, W., Steegborn, C. Description: Human Sirt6 in complex with ADP-ribose and the activator cyanidin [[Category: Unreleas...

OCA — Wed, 09 Jan 2019 05:08:50 GMT

New page: '''Unreleased structure''' The entry 6qch is ON HOLD Authors: You, W., Steegborn, C. Description: Human Sirt6 in complex with ADP-ribose and the activator cyanidin [[Category: Unreleas...

New page

'''Unreleased structure'''

The entry 6qch is ON HOLD

Authors: You, W., Steegborn, C.

Description: Human Sirt6 in complex with ADP-ribose and the activator cyanidin
[[Category: Unreleased Structures]]
[[Category: You, W]]
[[Category: Steegborn, C]]