6zu4 - Revision history

OCA at 11:58, 1 February 2024

OCA — Thu, 01 Feb 2024 11:58:24 GMT

←Older revision		Revision as of 11:58, 1 February 2024
Line 3:		Line 3:
	<StructureSection load='6zu4' size='340' side='right'caption='[[6zu4]], [[Resolution\|resolution]] 2.46Å' scene=''>		<StructureSection load='6zu4' size='340' side='right'caption='[[6zu4]], [[Resolution\|resolution]] 2.46Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6zu4]] 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=6ZU4 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6ZU4 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6zu4]] 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=6ZU4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZU4 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=115:(3R,5S,6E)-7-[3-(4-FLUOROPHENYL)-1-(PROPAN-2-YL)-1H-INDOL-2-YL]-3,5-DIHYDROXYHEPT-6-ENOIC+ACID'>115</scene>, <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=GOL:GLYCEROL'>GOL</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]] 2.46Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SIRT6, SIR2L6 ([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=115:(3R,5S,6E)-7-[3-(4-FLUOROPHENYL)-1-(PROPAN-2-YL)-1H-INDOL-2-YL]-3,5-DIHYDROXYHEPT-6-ENOIC+ACID'>115</scene>, <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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.286 2.3.1.286] </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=6zu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zu4 OCA], [https://pdbe.org/6zu4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zu4 RCSB], [https://www.ebi.ac.uk/pdbsum/6zu4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zu4 ProSAT]</span></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=6zu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zu4 OCA], [~~http~~://pdbe.org/6zu4 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6zu4 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6zu4 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6zu4 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;">
		+	== Publication Abstract from PubMed ==
		+	Sirtuins are NAD(+)-dependent protein lysine deacylases that are considered attractive drug targets for aging-related diseases. Sirt6 deacetylates, e.g., transcription factors and histone H3, and regulates metabolic processes and stress responses. It has been implicated in lifespan extension and tumor suppression. Sirt6 deacetylase activity can be stimulated with small molecules, and fluvastatin, an FDA-approved synthetic statin, was recently described as a novel Sirt6 activator. We studied the molecular details of this effect on Sirt6 in deacylation assays and by solving a crystal structure of a Sirt6/fluvastatin complex. We find that fluvastatin inhibits Sirt1-3 at higher concentrations but has a unique, activating effect on Sirt6. The complex structure reveals that fluvastatin occupies the Sirt6 substrate acyl channel exit, similar to other, unrelated activator families, providing interaction details that will support the development of potent, druglike Sirt6 activators.
		+
		+	Structural Basis for Activation of Human Sirtuin 6 by Fluvastatin.,You W, Steegborn C ACS Med Chem Lett. 2020 Sep 24;11(11):2285-2289. doi: , 10.1021/acsmedchemlett.0c00407. eCollection 2020 Nov 12. PMID:33214841<ref>PMID:33214841</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6zu4" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Histone deacetylase 3D structures\|Histone deacetylase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Transferase]]~~	+	[[Category: Steegborn C]]
-	[[Category: Steegborn, C]]	+	[[Category: You W]]
-	[[Category: You, W]]	+
-	~~[[Category: Activator]]~~	+
-	~~[[Category: Allosteric]]~~	+
-	~~[[Category: Deacylase]]~~	+
-	~~[[Category: Hydrolase~~]]	+

OCA at 08:19, 2 December 2020

OCA — Wed, 02 Dec 2020 08:19:26 GMT

←Older revision		Revision as of 08:19, 2 December 2020
Line 1:		Line 1:

	==Human Sirt6 13-308 in complex with ADP-ribose and the activator fluvastatin==		==Human Sirt6 13-308 in complex with ADP-ribose and the activator fluvastatin==
-	<StructureSection load='6zu4' size='340' side='right'caption='[[6zu4]]' scene=''>	+	<StructureSection load='6zu4' size='340' side='right'caption='[[6zu4]], [[Resolution\|resolution]] 2.46Å' 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=6ZU4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6ZU4 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6zu4]] 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=6ZU4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6ZU4 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=6zu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zu4 OCA], [http://pdbe.org/6zu4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6zu4 RCSB], [http://www.ebi.ac.uk/pdbsum/6zu4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6zu4 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=115:(3R,5S,6E)-7-[3-(4-FLUOROPHENYL)-1-(PROPAN-2-YL)-1H-INDOL-2-YL]-3,5-DIHYDROXYHEPT-6-ENOIC+ACID'>115</scene>, <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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">SIRT6, SIR2L6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.286 2.3.1.286] </span></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=6zu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zu4 OCA], [http://pdbe.org/6zu4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6zu4 RCSB], [http://www.ebi.ac.uk/pdbsum/6zu4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6zu4 ProSAT]</span></td></tr>
	</table>		</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>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Steegborn C]]	+	[[Category: Transferase]]
-	[[Category: You W]]	+	[[Category: Steegborn, C]]
		+	[[Category: You, W]]
		+	[[Category: Activator]]
		+	[[Category: Allosteric]]
		+	[[Category: Deacylase]]
		+	[[Category: Hydrolase]]

OCA at 09:39, 18 November 2020

OCA — Wed, 18 Nov 2020 09:39:43 GMT

←Older revision		Revision as of 09:39, 18 November 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6zu4 ~~is ON HOLD until Paper Publication~~	+	==Human Sirt6 13-308 in complex with ADP-ribose and the activator fluvastatin==
-		+	<StructureSection load='6zu4' size='340' side='right'caption='[[6zu4]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZU4 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6ZU4 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=6zu4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zu4 OCA], [http://pdbe.org/6zu4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6zu4 RCSB], [http://www.ebi.ac.uk/pdbsum/6zu4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6zu4 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Steegborn C]]
		+	[[Category: You W]]

OCA at 03:57, 5 August 2020

OCA — Wed, 05 Aug 2020 03:57:57 GMT

←Older revision		Revision as of 03:57, 5 August 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6zu4 is ON HOLD	+	The entry 6zu4 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6zu4" [edit=sysop:move=sysop]

OCA — Wed, 29 Jul 2020 09:35:37 GMT

Protected "6zu4" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:35, 29 July 2020

OCA: New page: '''Unreleased structure''' The entry 6zu4 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 29 Jul 2020 09:35:36 GMT

New page: '''Unreleased structure''' The entry 6zu4 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6zu4 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]