5zqo - Revision history

OCA at 09:03, 22 November 2023

OCA — Wed, 22 Nov 2023 09:03:56 GMT

←Older revision		Revision as of 09:03, 22 November 2023
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	<StructureSection load='5zqo' size='340' side='right'caption='[[5zqo]], [[Resolution\|resolution]] 2.06Å' scene=''>		<StructureSection load='5zqo' size='340' side='right'caption='[[5zqo]], [[Resolution\|resolution]] 2.06Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5zqo]] 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=5ZQO OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5ZQO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5zqo]] 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=5ZQO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZQO FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9GX:2-[4-(2-methoxyphenyl)piperazin-1-yl]-5,6,7,8-tetrahydroquinazolin-4(3H)-one'>9GX</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]] 2.06Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TNKS2, PARP5B, TANK2, TNKL ([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=9GX:2-[4-(2-methoxyphenyl)piperazin-1-yl]-5,6,7,8-tetrahydroquinazolin-4(3H)-one'>9GX</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/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </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=5zqo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zqo OCA], [https://pdbe.org/5zqo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zqo RCSB], [https://www.ebi.ac.uk/pdbsum/5zqo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zqo ProSAT]</span></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=5zqo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zqo OCA], [~~http~~://pdbe.org/5zqo PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5zqo RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5zqo PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5zqo ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/TNKS2_HUMAN TNKS2_HUMAN]] Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking. Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates poly-ADP-ribosylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates poly-ADP-ribosylation of TERF1, thereby contributing to the regulation of telomere length. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles.<ref>PMID:11802774</ref> <ref>PMID:11739745</ref> <ref>PMID:19759537</ref> <ref>PMID:21478859</ref>	+	[https://www.uniprot.org/uniprot/TNKS2_HUMAN TNKS2_HUMAN] Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking. Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates poly-ADP-ribosylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates poly-ADP-ribosylation of TERF1, thereby contributing to the regulation of telomere length. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles.<ref>PMID:11802774</ref> <ref>PMID:11739745</ref> <ref>PMID:19759537</ref> <ref>PMID:21478859</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 5zqo" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5zqo" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Ankyrin 3D structures\|Ankyrin 3D structures]]
		+	*[[Poly(ADP-ribose) polymerase 3D structures\|Poly(ADP-ribose) polymerase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Niwa, H]]	+	[[Category: Niwa H]]
-	[[Category: Okue, M]]	+	[[Category: Okue M]]
-	[[Category: Sato, S]]	+	[[Category: Sato S]]
-	[[Category: Seimiya, H]]	+	[[Category: Seimiya H]]
-	[[Category: Shirai, F]]	+	[[Category: Shirai F]]
-	[[Category: Shirouzu, M]]	+	[[Category: Shirouzu M]]
-	[[Category: Tsumura, T]]	+	[[Category: Tsumura T]]
-	[[Category: Umehara, T]]	+	[[Category: Umehara T]]
-	[[Category: Yoshimoto, N]]	+	[[Category: Yoshimoto N]]
-	~~[[Category: Adp-ribosylation]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Parp]]~~	+
-	~~[[Category: Tankyrase]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 07:44, 24 April 2019

OCA — Wed, 24 Apr 2019 07:44:21 GMT

←Older revision		Revision as of 07:44, 24 April 2019
Line 3:		Line 3:
	<StructureSection load='5zqo' size='340' side='right'caption='[[5zqo]], [[Resolution\|resolution]] 2.06Å' scene=''>		<StructureSection load='5zqo' size='340' side='right'caption='[[5zqo]], [[Resolution\|resolution]] 2.06Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5zqo]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZQO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZQO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5zqo]] 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=5ZQO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZQO FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9GX:2-[4-(2-methoxyphenyl)piperazin-1-yl]-5,6,7,8-tetrahydroquinazolin-4(3H)-one'>9GX</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9GX:2-[4-(2-methoxyphenyl)piperazin-1-yl]-5,6,7,8-tetrahydroquinazolin-4(3H)-one'>9GX</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">TNKS2, PARP5B, TANK2, TNKL ([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/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </span></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=5zqo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zqo OCA], [http://pdbe.org/5zqo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zqo RCSB], [http://www.ebi.ac.uk/pdbsum/5zqo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zqo ProSAT]</span></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=5zqo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zqo OCA], [http://pdbe.org/5zqo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zqo RCSB], [http://www.ebi.ac.uk/pdbsum/5zqo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zqo ProSAT]</span></td></tr>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Niwa, H]]		[[Category: Niwa, H]]

OCA at 06:49, 3 April 2019

OCA — Wed, 03 Apr 2019 06:49:13 GMT

←Older revision		Revision as of 06:49, 3 April 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5zqo is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Tankyrase-2 in complex with compound 1a==
		+	<StructureSection load='5zqo' size='340' side='right'caption='[[5zqo]], [[Resolution\|resolution]] 2.06Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5zqo]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZQO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZQO FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9GX:2-[4-(2-methoxyphenyl)piperazin-1-yl]-5,6,7,8-tetrahydroquinazolin-4(3H)-one'>9GX</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/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </span></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=5zqo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zqo OCA], [http://pdbe.org/5zqo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zqo RCSB], [http://www.ebi.ac.uk/pdbsum/5zqo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zqo ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/TNKS2_HUMAN TNKS2_HUMAN]] Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking. Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates poly-ADP-ribosylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates poly-ADP-ribosylation of TERF1, thereby contributing to the regulation of telomere length. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles.<ref>PMID:11802774</ref> <ref>PMID:11739745</ref> <ref>PMID:19759537</ref> <ref>PMID:21478859</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The canonical WNT pathway plays an important role in cancer pathogenesis. Inhibition of poly(ADP-ribose) polymerase catalytic activity of the tankyrases (TNKS/TNKS2) has been reported to reduce the Wnt/beta-catenin signal by preventing poly ADP-ribosylation-dependent degradation of AXIN, a negative regulator of Wnt/beta-catenin signaling. With the goal of investigating the effects of tankyrase and Wnt pathway inhibition on tumor growth, we set out to find small-molecule inhibitors of TNKS/TNKS2 with suitable drug-like properties. Starting from 1a, a high-throughput screening hit, the spiroindoline derivative 40c (RK-287107) was discovered as a potent TNKS/TNKS2 inhibitor with >7000-fold selectivity against the PARP1 enzyme, which inhibits WNT-responsive TCF reporter activity and proliferation of human colorectal cancer cell line COLO-320DM. RK-287107 also demonstrated dose-dependent tumor growth inhibition in a mouse xenograft model. These observations suggest that RK-287107 is a promising lead compound for the development of novel tankyrase inhibitors as anticancer agents.

-	~~Authors~~:	+	Discovery of Novel Spiroindoline Derivatives as Selective Tankyrase Inhibitors.,Shirai F, Tsumura T, Yashiroda Y, Yuki H, Niwa H, Sato S, Chikada T, Koda Y, Washizuka K, Yoshimoto N, Abe M, Onuki T, Mazaki Y, Hirama C, Fukami T, Watanabe H, Honma T, Umehara T, Shirouzu M, Okue M, Kano Y, Watanabe T, Kitamura K, Shitara E, Muramatsu Y, Yoshida H, Mizutani A, Seimiya H, Yoshida M, Koyama H J Med Chem. 2019 Apr 1. doi: 10.1021/acs.jmedchem.8b01888. PMID:30883102<ref>PMID:30883102</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 5zqo" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Niwa, H]]
		+	[[Category: Okue, M]]
		+	[[Category: Sato, S]]
		+	[[Category: Seimiya, H]]
		+	[[Category: Shirai, F]]
		+	[[Category: Shirouzu, M]]
		+	[[Category: Tsumura, T]]
		+	[[Category: Umehara, T]]
		+	[[Category: Yoshimoto, N]]
		+	[[Category: Adp-ribosylation]]
		+	[[Category: Inhibitor]]
		+	[[Category: Parp]]
		+	[[Category: Tankyrase]]
		+	[[Category: Transferase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 04:06, 6 June 2018

OCA — Wed, 06 Jun 2018 04:06:59 GMT

←Older revision		Revision as of 04:06, 6 June 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5zqo is ON HOLD	+	The entry 5zqo is ON HOLD until Paper Publication

	Authors:		Authors:

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

OCA — Wed, 25 Apr 2018 03:56:10 GMT

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

←Older revision

Revision as of 03:56, 25 April 2018

OCA: New page: '''Unreleased structure''' The entry 5zqo is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 25 Apr 2018 03:56:09 GMT

New page: '''Unreleased structure''' The entry 5zqo is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5zqo is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]