5nwd - Revision history

OCA at 12:12, 22 November 2023

OCA — Wed, 22 Nov 2023 12:12:10 GMT

←Older revision		Revision as of 12:12, 22 November 2023
Line 3:		Line 3:
	<StructureSection load='5nwd' size='340' side='right'caption='[[5nwd]], [[Resolution\|resolution]] 1.45Å' scene=''>		<StructureSection load='5nwd' size='340' side='right'caption='[[5nwd]], [[Resolution\|resolution]] 1.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5nwd]] 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=5NWD OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5NWD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5nwd]] 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=5NWD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NWD FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9C8:2-[4-(diethylamino)phenyl]-3~{H}-quinazolin-4-one'>9C8</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]] 1.45Å</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=9C8:2-[4-(diethylamino)phenyl]-3~{H}-quinazolin-4-one'>9C8</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=5nwd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nwd OCA], [https://pdbe.org/5nwd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nwd RCSB], [https://www.ebi.ac.uk/pdbsum/5nwd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nwd 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=5nwd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nwd OCA], [~~http~~://pdbe.org/5nwd PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5nwd RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5nwd PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5nwd 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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	==See Also==		==See Also==
-	*[[Poly (ADP-ribose) polymerase\|Poly (ADP-ribose) polymerase]]	+	*[[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: Haikarainen, T]]	+	[[Category: Haikarainen T]]
-	[[Category: Lehtio, L]]	+	[[Category: Lehtio L]]
-	[[Category: Nkizinkiko, Y]]	+	[[Category: Nkizinkiko Y]]
-	~~[[Category: Adp-ribosyltransferase]]~~	+
-	~~[[Category: Artd6]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Parp5b]]~~	+
-	~~[[Category: Tankyrase]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 06:49, 16 October 2019

OCA — Wed, 16 Oct 2019 06:49:16 GMT

←Older revision		Revision as of 06:49, 16 October 2019
Line 1:		Line 1:

	==Crystal structure of TNKS2 in complex with 2-[4-(diethylamino)phenyl]-3,4-dihydroquinazolin-4-one==		==Crystal structure of TNKS2 in complex with 2-[4-(diethylamino)phenyl]-3,4-dihydroquinazolin-4-one==
-	<StructureSection load='5nwd' size='340' side='right' caption='[[5nwd]], [[Resolution\|resolution]] 1.45Å' scene=''>	+	<StructureSection load='5nwd' size='340' side='right'caption='[[5nwd]], [[Resolution\|resolution]] 1.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5nwd]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NWD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NWD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5nwd]] 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=5NWD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NWD FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9C8:2-[4-(diethylamino)phenyl]-3~{H}-quinazolin-4-one'>9C8</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=9C8:2-[4-(diethylamino)phenyl]-3~{H}-quinazolin-4-one'>9C8</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=5nwd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nwd OCA], [http://pdbe.org/5nwd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nwd RCSB], [http://www.ebi.ac.uk/pdbsum/5nwd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nwd 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=5nwd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nwd OCA], [http://pdbe.org/5nwd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nwd RCSB], [http://www.ebi.ac.uk/pdbsum/5nwd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nwd ProSAT]</span></td></tr>
Line 19:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 5nwd" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5nwd" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Poly (ADP-ribose) polymerase\|Poly (ADP-ribose) polymerase]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Haikarainen, T]]		[[Category: Haikarainen, T]]
	[[Category: Lehtio, L]]		[[Category: Lehtio, L]]

OCA at 06:21, 14 March 2018

OCA — Wed, 14 Mar 2018 06:21:01 GMT

←Older revision		Revision as of 06:21, 14 March 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5nwd is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of TNKS2 in complex with 2-[4-(diethylamino)phenyl]-3,4-dihydroquinazolin-4-one==
		+	<StructureSection load='5nwd' size='340' side='right' caption='[[5nwd]], [[Resolution\|resolution]] 1.45Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5nwd]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NWD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NWD FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9C8:2-[4-(diethylamino)phenyl]-3~{H}-quinazolin-4-one'>9C8</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=5nwd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nwd OCA], [http://pdbe.org/5nwd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nwd RCSB], [http://www.ebi.ac.uk/pdbsum/5nwd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nwd 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: Nkizinkiko~~, Y., Haikarainen, T., ~~Lehtio~~, L.	+	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: Crystal structure~~ of ~~TNKS2 in complex with 2~~-[4-~~(diethylamino)phenyl]-3,4-dihydroquinazolin-4-one~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5nwd" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Haikarainen, T]]
	[[Category: Lehtio, L]]		[[Category: Lehtio, L]]
	[[Category: Nkizinkiko, Y]]		[[Category: Nkizinkiko, Y]]
-	[[Category: ~~Haikarainen, T~~]]	+	[[Category: Adp-ribosyltransferase]]
		+	[[Category: Artd6]]
		+	[[Category: Inhibitor]]
		+	[[Category: Parp5b]]
		+	[[Category: Tankyrase]]
		+	[[Category: Transferase]]

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

OCA — Wed, 17 May 2017 12:21:09 GMT

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

←Older revision

Revision as of 12:21, 17 May 2017

OCA: New page: '''Unreleased structure''' The entry 5nwd is ON HOLD until Paper Publication Authors: Nkizinkiko, Y., Haikarainen, T., Lehtio, L. Description: Crystal structure of TNKS2 in complex wit...

OCA — Wed, 17 May 2017 12:21:08 GMT

New page: '''Unreleased structure''' The entry 5nwd is ON HOLD until Paper Publication Authors: Nkizinkiko, Y., Haikarainen, T., Lehtio, L. Description: Crystal structure of TNKS2 in complex wit...

New page

'''Unreleased structure'''

The entry 5nwd is ON HOLD until Paper Publication

Authors: Nkizinkiko, Y., Haikarainen, T., Lehtio, L.

Description: Crystal structure of TNKS2 in complex with 2-[4-(diethylamino)phenyl]-3,4-dihydroquinazolin-4-one
[[Category: Unreleased Structures]]
[[Category: Lehtio, L]]
[[Category: Nkizinkiko, Y]]
[[Category: Haikarainen, T]]