5nsx - Revision history

OCA at 12:07, 22 November 2023

OCA — Wed, 22 Nov 2023 12:07:16 GMT

←Older revision		Revision as of 12:07, 22 November 2023
Line 3:		Line 3:
	<StructureSection load='5nsx' size='340' side='right'caption='[[5nsx]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='5nsx' size='340' side='right'caption='[[5nsx]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5nsx]] is a 4 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=5NSX OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5NSX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5nsx]] is a 4 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=5NSX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NSX FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=97K:2-(2~{H}-indazol-5-yl)-3~{H}-quinazolin-4-one'>97K</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]] 1.8Å</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=97K:2-(2~{H}-indazol-5-yl)-3~{H}-quinazolin-4-one'>97K</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=5nsx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nsx OCA], [https://pdbe.org/5nsx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nsx RCSB], [https://www.ebi.ac.uk/pdbsum/5nsx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nsx 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=5nsx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nsx OCA], [~~http~~://pdbe.org/5nsx PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5nsx RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5nsx PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5nsx 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 ==
Line 22:		Line 21:

	==See Also==		==See Also==
-	*[[Growth differentiation factor 3D STRUCTURES\|Growth differentiation factor 3D STRUCTURES]]	+	*[[Poly(ADP-ribose) polymerase 3D structures\|Poly(ADP-ribose) polymerase 3D structures]]
-	*[[Poly (ADP-ribose) polymerase\|Poly (ADP-ribose) polymerase]]	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Haikarainen, T]]	+	[[Category: Haikarainen T]]
-	[[Category: Lehtio, L]]	+	[[Category: Lehtio L]]
-	[[Category: Nkizinkiko, Y]]	+	[[Category: Nkizinkiko Y]]
-	~~[[Category: Artd6]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Parp5b]]~~	+
-	~~[[Category: Tankyrase]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 06:47, 16 October 2019

OCA — Wed, 16 Oct 2019 06:47:45 GMT

←Older revision		Revision as of 06:47, 16 October 2019
Line 1:		Line 1:

	==Crystal structure of TNKS2 in complex with 2-(1H-indazol-5-yl)-3,4-dihydroquinazolin-4-one==		==Crystal structure of TNKS2 in complex with 2-(1H-indazol-5-yl)-3,4-dihydroquinazolin-4-one==
-	<StructureSection load='5nsx' size='340' side='right' caption='[[5nsx]], [[Resolution\|resolution]] 1.80Å' scene=''>	+	<StructureSection load='5nsx' size='340' side='right'caption='[[5nsx]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5nsx]] is a 4 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=5NSX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NSX FirstGlance]. <br>		<table><tr><td colspan='2'>[[5nsx]] is a 4 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=5NSX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NSX FirstGlance]. <br>
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 5nsx" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5nsx" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Growth differentiation factor 3D STRUCTURES\|Growth differentiation factor 3D STRUCTURES]]
		+	*[[Poly (ADP-ribose) polymerase\|Poly (ADP-ribose) polymerase]]
	== References ==		== References ==
	<references/>		<references/>
Line 25:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Haikarainen, T]]		[[Category: Haikarainen, T]]
	[[Category: Lehtio, L]]		[[Category: Lehtio, L]]

OCA at 14:06, 11 April 2018

OCA — Wed, 11 Apr 2018 14:06:48 GMT

←Older revision		Revision as of 14:06, 11 April 2018
Line 3:		Line 3:
	<StructureSection load='5nsx' size='340' side='right' caption='[[5nsx]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='5nsx' size='340' side='right' caption='[[5nsx]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5nsx]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NSX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NSX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5nsx]] is a 4 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=5NSX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NSX FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=97K:2-(2~{H}-indazol-5-yl)-3~{H}-quinazolin-4-one'>97K</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=97K:2-(2~{H}-indazol-5-yl)-3~{H}-quinazolin-4-one'>97K</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=5nsx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nsx OCA], [http://pdbe.org/5nsx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nsx RCSB], [http://www.ebi.ac.uk/pdbsum/5nsx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nsx 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=5nsx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nsx OCA], [http://pdbe.org/5nsx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nsx RCSB], [http://www.ebi.ac.uk/pdbsum/5nsx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nsx ProSAT]</span></td></tr>
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Haikarainen, T]]		[[Category: Haikarainen, T]]
	[[Category: Lehtio, L]]		[[Category: Lehtio, L]]

OCA at 04:58, 8 March 2018

OCA — Thu, 08 Mar 2018 04:58:52 GMT

←Older revision		Revision as of 04:58, 8 March 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5nsx is ~~ON HOLD~~	+	==Crystal structure of TNKS2 in complex with 2-(1H-indazol-5-yl)-3,4-dihydroquinazolin-4-one==
		+	<StructureSection load='5nsx' size='340' side='right' caption='[[5nsx]], [[Resolution\|resolution]] 1.80Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5nsx]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NSX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NSX FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=97K:2-(2~{H}-indazol-5-yl)-3~{H}-quinazolin-4-one'>97K</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=5nsx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nsx OCA], [http://pdbe.org/5nsx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nsx RCSB], [http://www.ebi.ac.uk/pdbsum/5nsx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nsx 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 ==
		+	Tankyrases (TNKSs) are enzymes specialized in catalyzing poly-ADP-ribosylation of target proteins. Several studies have validated TNKSs as anti-cancer drug targets due to their regulatory role in Wnt/beta-catenin pathway. Recently a lot of effort has been put into developing more potent and selective TNKS inhibitors and optimizing them towards anti-cancer agents. We noticed that some 2-phenylquinazolinones (2-PQs) reported as CDK9 inhibitors were similar to previously published TNKS inhibitors. In this study, we profiled this series of 2-PQs against TNKS and selected kinases that are involved in the Wnt/beta-catenin pathway. We found that they were much more potent TNKS inhibitors than they were CDK9/kinase inhibitors. We evaluated the compound selectivity to tankyrases over the ARTD enzyme family and solved co-crystal structures of the compounds with TNKS2. Comparative structure-based studies of the catalytic domain of TNKS2 with selected CDK9 inhibitors and docking studies of the inhibitors with two kinases (CDK9 and Akt) revealed important structural features, which could explain the selectivity of the compounds towards either tankyrases or kinases. We also discovered a compound, which was able to inhibit tankyrases, CDK9 and Akt kinases with equal microM potency.

-	~~Authors~~:	+	2-Phenylquinazolinones as dual-activity tankyrase-kinase inhibitors.,Nkizinkiko Y, Desantis J, Koivunen J, Haikarainen T, Murthy S, Sancineto L, Massari S, Ianni F, Obaji E, Loza MI, Pihlajaniemi T, Brea J, Tabarrini O, Lehtio L Sci Rep. 2018 Jan 26;8(1):1680. doi: 10.1038/s41598-018-19872-3. PMID:29374194<ref>PMID:29374194</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5nsx" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Haikarainen, T]]
		+	[[Category: Lehtio, L]]
		+	[[Category: Nkizinkiko, Y]]
		+	[[Category: Artd6]]
		+	[[Category: Inhibitor]]
		+	[[Category: Parp5b]]
		+	[[Category: Tankyrase]]
		+	[[Category: Transferase]]

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

OCA — Thu, 04 May 2017 09:41:23 GMT

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

←Older revision

Revision as of 09:41, 4 May 2017

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

OCA — Thu, 04 May 2017 09:41:22 GMT

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

New page

'''Unreleased structure'''

The entry 5nsx is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]