5mfp - Revision history

OCA at 18:42, 1 November 2023

OCA — Wed, 01 Nov 2023 18:42:20 GMT

←Older revision		Revision as of 18:42, 1 November 2023
Line 3:		Line 3:
	<StructureSection load='5mfp' size='340' side='right'caption='[[5mfp]], [[Resolution\|resolution]] 1.98Å' scene=''>		<StructureSection load='5mfp' size='340' side='right'caption='[[5mfp]], [[Resolution\|resolution]] 1.98Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5mfp]] 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=5MFP OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5MFP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5mfp]] 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=5MFP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MFP FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7M5:4-PYRIDIN-3-YLPYRROLO[1,2-A]QUINOXALINE'>7M5</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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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]] 1.98Å</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=7M5:4-PYRIDIN-3-YLPYRROLO[1,2-A]QUINOXALINE'>7M5</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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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~~://proteopedia.org/fgij/fg.htm?mol=5mfp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mfp OCA], [~~http~~://pdbe.org/5mfp PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5mfp RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5mfp PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5mfp 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=5mfp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mfp OCA], [https://pdbe.org/5mfp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mfp RCSB], [https://www.ebi.ac.uk/pdbsum/5mfp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mfp 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 ==
Line 26:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Kambach, C]]	+	[[Category: Kambach C]]
-	[[Category: Steegborn, C]]	+	[[Category: Steegborn C]]
-	[[Category: You, W]]	+	[[Category: You W]]
-	~~[[Category: Drug]]~~	+
-	~~[[Category: Hydrolase~~]]	+

OCA at 07:18, 19 August 2020

OCA — Wed, 19 Aug 2020 07:18:20 GMT

←Older revision		Revision as of 07:18, 19 August 2020
Line 1:		Line 1:

	==Human Sirt6 in complex with activator UBCS58==		==Human Sirt6 in complex with activator UBCS58==
-	<StructureSection load='5mfp' size='340' side='right' caption='[[5mfp]], [[Resolution\|resolution]] 1.98Å' scene=''>	+	<StructureSection load='5mfp' size='340' side='right'caption='[[5mfp]], [[Resolution\|resolution]] 1.98Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5mfp]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MFP OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5MFP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5mfp]] 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=5MFP OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5MFP FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7M5:4-PYRIDIN-3-YLPYRROLO[1,2-A]QUINOXALINE'>7M5</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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7M5:4-PYRIDIN-3-YLPYRROLO[1,2-A]QUINOXALINE'>7M5</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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=5mfp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mfp OCA], [http://pdbe.org/5mfp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mfp RCSB], [http://www.ebi.ac.uk/pdbsum/5mfp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mfp ProSAT]</span></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5mfp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mfp OCA], [http://pdbe.org/5mfp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mfp RCSB], [http://www.ebi.ac.uk/pdbsum/5mfp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mfp ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5mfp" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5mfp" 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: Large Structures]]
	[[Category: Kambach, C]]		[[Category: Kambach, C]]
	[[Category: Steegborn, C]]		[[Category: Steegborn, C]]

OCA at 16:18, 2 January 2017

OCA — Mon, 02 Jan 2017 16:18:35 GMT

←Older revision		Revision as of 16:18, 2 January 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5mfp is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Human Sirt6 in complex with activator UBCS58==
		+	<StructureSection load='5mfp' size='340' side='right' caption='[[5mfp]], [[Resolution\|resolution]] 1.98Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5mfp]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MFP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MFP FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7M5:4-PYRIDIN-3-YLPYRROLO[1,2-A]QUINOXALINE'>7M5</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=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=5mfp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mfp OCA], [http://pdbe.org/5mfp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mfp RCSB], [http://www.ebi.ac.uk/pdbsum/5mfp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mfp 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 ==
		+	Sirtuins are protein deacylases regulating metabolism and stress responses, and are implicated in aging-related diseases. Small molecule activators for the human sirtuins Sirt1-7 are sought as chemical tools and potential therapeutics, such as for cancer. Activators are available for Sirt1 and exploit its unique N-terminus, whereas drug-like activators for Sirt2-7 are lacking. We synthesized and screened pyrrolo[1,2-a]quinoxaline derivatives, yielding the first synthetic Sirt6 activators. Biochemical assays show direct, substrate-independent compound binding to the Sirt6 catalytic core and potent activation of Sirt6-dependent deacetylation of peptide substrates and complete nucleosomes. Crystal structures of Sirt6/activator complexes reveal that the compounds bind to a Sirt6-specific acyl channel pocket and identify key interactions. Our results establish potent Sirt6 activation with small molecules and provide a structural basis for further development of Sirt6 activators as tools and therapeutics.

-	~~Authors: Steegborn, C~~., You, W., Kambach, C.	+	Structural Basis of Sirtuin 6 Activation by Synthetic Small Molecules.,You W, Rotili D, Li TM, Kambach C, Meleshin M, Schutkowski M, Chua KF, Mai A, Steegborn C Angew Chem Int Ed Engl. 2016 Dec 19. doi: 10.1002/anie.201610082. PMID:27990725<ref>PMID:27990725</ref>

-	~~Description: Human Sirt6 in complex with activator UBCS58~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
		+	<div class="pdbe-citations 5mfp" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Kambach, C]]		[[Category: Kambach, C]]
	[[Category: Steegborn, C]]		[[Category: Steegborn, C]]
	[[Category: You, W]]		[[Category: You, W]]
		+	[[Category: Drug]]
		+	[[Category: Hydrolase]]

OCA: Protected "5mfp" [edit=sysop:move=sysop]

OCA — Fri, 09 Dec 2016 16:47:02 GMT

Protected "5mfp" [edit=sysop:move=sysop]

←Older revision

Revision as of 16:47, 9 December 2016

OCA: New page: '''Unreleased structure''' The entry 5mfp is ON HOLD until Paper Publication Authors: Steegborn, C., You, W., Kambach, C. Description: Human Sirt6 in complex with activator UBCS58 [[Ca...

OCA — Fri, 09 Dec 2016 16:47:00 GMT

New page: '''Unreleased structure''' The entry 5mfp is ON HOLD until Paper Publication Authors: Steegborn, C., You, W., Kambach, C. Description: Human Sirt6 in complex with activator UBCS58 [[Ca...

New page

'''Unreleased structure'''

The entry 5mfp is ON HOLD until Paper Publication

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

Description: Human Sirt6 in complex with activator UBCS58
[[Category: Unreleased Structures]]
[[Category: Kambach, C]]
[[Category: Steegborn, C]]
[[Category: You, W]]