4but - Revision history

OCA at 11:05, 9 May 2024

OCA — Thu, 09 May 2024 11:05:45 GMT

←Older revision		Revision as of 11:05, 9 May 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4but]] 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=4BUT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BUT FirstGlance]. <br>		<table><tr><td colspan='2'>[[4but]] 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=4BUT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BUT FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=31F:4-(4-OXIDANYLIDENE-3H-QUINAZOLIN-2-YL)BENZENESULFONAMIDE'>31F</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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]] 1.9Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=31F:4-(4-OXIDANYLIDENE-3H-QUINAZOLIN-2-YL)BENZENESULFONAMIDE'>31F</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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'>[https://proteopedia.org/fgij/fg.htm?mol=4but FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4but OCA], [https://pdbe.org/4but PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4but RCSB], [https://www.ebi.ac.uk/pdbsum/4but PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4but 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=4but FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4but OCA], [https://pdbe.org/4but PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4but RCSB], [https://www.ebi.ac.uk/pdbsum/4but PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4but ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[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>	+	[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;">
		+	== Publication Abstract from PubMed ==
		+	Human tankyrases are attractive drug targets, especially for the treatment of cancer. We identified a set of highly potent tankyrase inhibitors based on a 2-phenyl-3,4-dihydroquinazolin-4-one scaffold. Substitutions at the para position of the scaffold's phenyl group were evaluated as a strategy to increase potency and improve selectivity. The best compounds displayed single-digit nanomolar potencies, and profiling against several human diphtheria-toxin-like ADP-ribosyltransferases revealed that a subset of these compounds are highly selective tankyrase inhibitors. The compounds also effectively inhibit Wnt signaling in HEK293 cells. The binding mode of all inhibitors was studied by protein X-ray crystallography. This allowed us to establish a structural basis for the development of highly potent and selective tankyrase inhibitors based on the 2-phenyl-3,4-dihydroquinazolin-4-one scaffold and outline a rational approach to the modification of other inhibitor scaffolds that bind to the nicotinamide site of the catalytic domain.
		+
		+	para-Substituted 2-Phenyl-3,4-dihydroquinazolin-4-ones As Potent and Selective Tankyrase Inhibitors.,Haikarainen T, Koivunen J, Narwal M, Venkannagari H, Obaji E, Joensuu P, Pihlajaniemi T, Lehtio L ChemMedChem. 2013 Oct 15. doi: 10.1002/cmdc.201300337. PMID:24130191<ref>PMID:24130191</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 4but" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 17:09, 7 September 2022

OCA — Wed, 07 Sep 2022 17:09:23 GMT

←Older revision		Revision as of 17:09, 7 September 2022
Line 3:		Line 3:
	<StructureSection load='4but' size='340' side='right'caption='[[4but]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='4but' size='340' side='right'caption='[[4but]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4but]] 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=4BUT OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=4BUT FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4but]] 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=4BUT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BUT FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=31F:4-(4-OXIDANYLIDENE-3H-QUINAZOLIN-2-YL)BENZENESULFONAMIDE'>31F</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=31F:4-(4-OXIDANYLIDENE-3H-QUINAZOLIN-2-YL)BENZENESULFONAMIDE'>31F</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4bu3\|4bu3]], [[4bu5\|4bu5]], [[4bu6\|4bu6]], [[4bu7\|4bu7]], [[4bu8\|4bu8]], [[4bu9\|4bu9]], [[4bua\|4bua]], [[4bud\|4bud]], [[4bue\|4bue]], [[4buf\|4buf]], [[4bui\|4bui]], [[4bus\|4bus]], [[4buu\|4buu]], [[4buv\|4buv]], [[4buw\|4buw]], [[4bux\|4bux]], [[4buy\|4buy]]</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=4but FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4but OCA], [https://pdbe.org/4but PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4but RCSB], [https://www.ebi.ac.uk/pdbsum/4but PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4but ProSAT]</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~~://proteopedia.org/fgij/fg.htm?mol=4but FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4but OCA], [~~http~~://pdbe.org/4but PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4but RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4but PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4but 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;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Human tankyrases are attractive drug targets, especially for the treatment of cancer. We identified a set of highly potent tankyrase inhibitors based on a 2-phenyl-3,4-dihydroquinazolin-4-one scaffold. Substitutions at the para position of the scaffold's phenyl group were evaluated as a strategy to increase potency and improve selectivity. The best compounds displayed single-digit nanomolar potencies, and profiling against several human diphtheria-toxin-like ADP-ribosyltransferases revealed that a subset of these compounds are highly selective tankyrase inhibitors. The compounds also effectively inhibit Wnt signaling in HEK293 cells. The binding mode of all inhibitors was studied by protein X-ray crystallography. This allowed us to establish a structural basis for the development of highly potent and selective tankyrase inhibitors based on the 2-phenyl-3,4-dihydroquinazolin-4-one scaffold and outline a rational approach to the modification of other inhibitor scaffolds that bind to the nicotinamide site of the catalytic domain.	+
-		+
-	para-Substituted 2-Phenyl-3,4-dihydroquinazolin-4-ones As Potent and Selective Tankyrase Inhibitors.,Haikarainen T, Koivunen J, Narwal M, Venkannagari H, Obaji E, Joensuu P, Pihlajaniemi T, Lehtio L ChemMedChem. 2013 Oct 15. doi: 10.1002/cmdc.201300337. PMID:24130191<ref>PMID:24130191</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 4but" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
Line 27:		Line 16:
	__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: Narwal, M]]	+	[[Category: Narwal M]]
-	~~[[Category: Adp- ribosylation]]~~	+
-	~~[[Category: Diphtheria toxin like fold]]~~	+
-	~~[[Category: Protein-ligand complex]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 08:16, 4 November 2020

OCA — Wed, 04 Nov 2020 08:16:10 GMT

←Older revision		Revision as of 08:16, 4 November 2020
Line 1:		Line 1:

	==Crystal structure of human tankyrase 2 in complex with 4-(4-oxo-3,4- dihydroquinazolin-2-yl)benzene-1-sulfonamide==		==Crystal structure of human tankyrase 2 in complex with 4-(4-oxo-3,4- dihydroquinazolin-2-yl)benzene-1-sulfonamide==
-	<StructureSection load='4but' size='340' side='right' caption='[[4but]], [[Resolution\|resolution]] 1.90Å' scene=''>	+	<StructureSection load='4but' size='340' side='right'caption='[[4but]], [[Resolution\|resolution]] 1.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4but]] 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=4BUT OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4BUT FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4but]] 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=4BUT OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=4BUT FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=31F:4-(4-OXIDANYLIDENE-3H-QUINAZOLIN-2-YL)BENZENESULFONAMIDE'>31F</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=31F:4-(4-OXIDANYLIDENE-3H-QUINAZOLIN-2-YL)BENZENESULFONAMIDE'>31F</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4bu3\|4bu3]], [[4bu5\|4bu5]], [[4bu6\|4bu6]], [[4bu7\|4bu7]], [[4bu8\|4bu8]], [[4bu9\|4bu9]], [[4bua\|4bua]], [[4bud\|4bud]], [[4bue\|4bue]], [[4buf\|4buf]], [[4bui\|4bui]], [[4bus\|4bus]], [[4buu\|4buu]], [[4buv\|4buv]], [[4buw\|4buw]], [[4bux\|4bux]], [[4buy\|4buy]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4bu3\|4bu3]], [[4bu5\|4bu5]], [[4bu6\|4bu6]], [[4bu7\|4bu7]], [[4bu8\|4bu8]], [[4bu9\|4bu9]], [[4bua\|4bua]], [[4bud\|4bud]], [[4bue\|4bue]], [[4buf\|4buf]], [[4bui\|4bui]], [[4bus\|4bus]], [[4buu\|4buu]], [[4buv\|4buv]], [[4buw\|4buw]], [[4bux\|4bux]], [[4buy\|4buy]]</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=4but FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4but OCA], [http://pdbe.org/4but PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4but RCSB], [http://www.ebi.ac.uk/pdbsum/4but PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4but 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=4but FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4but OCA], [http://pdbe.org/4but PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4but RCSB], [http://www.ebi.ac.uk/pdbsum/4but PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4but ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 22:		Line 22:

	==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/>
Line 28:		Line 28:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Haikarainen, T]]		[[Category: Haikarainen, T]]
	[[Category: Lehtio, L]]		[[Category: Lehtio, L]]

OCA at 09:08, 30 January 2019

OCA — Wed, 30 Jan 2019 09:08:12 GMT

←Older revision		Revision as of 09:08, 30 January 2019
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 4but" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4but" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Poly (ADP-ribose) polymerase\|Poly (ADP-ribose) polymerase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:47, 17 January 2018

OCA — Wed, 17 Jan 2018 07:47:43 GMT

←Older revision		Revision as of 07:47, 17 January 2018
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 4but" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4but" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Poly (ADP-ribose) polymerase\|Poly (ADP-ribose) polymerase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 21:50, 5 August 2016

OCA — Fri, 05 Aug 2016 21:50:12 GMT

←Older revision		Revision as of 21:50, 5 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of human tankyrase 2 in complex with 4-(4-oxo-3,4- dihydroquinazolin-2-yl)benzene-1-sulfonamide==		==Crystal structure of human tankyrase 2 in complex with 4-(4-oxo-3,4- dihydroquinazolin-2-yl)benzene-1-sulfonamide==
	<StructureSection load='4but' size='340' side='right' caption='[[4but]], [[Resolution\|resolution]] 1.90Å' scene=''>		<StructureSection load='4but' size='340' side='right' caption='[[4but]], [[Resolution\|resolution]] 1.90Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4bu3\|4bu3]], [[4bu5\|4bu5]], [[4bu6\|4bu6]], [[4bu7\|4bu7]], [[4bu8\|4bu8]], [[4bu9\|4bu9]], [[4bua\|4bua]], [[4bud\|4bud]], [[4bue\|4bue]], [[4buf\|4buf]], [[4bui\|4bui]], [[4bus\|4bus]], [[4buu\|4buu]], [[4buv\|4buv]], [[4buw\|4buw]], [[4bux\|4bux]], [[4buy\|4buy]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4bu3\|4bu3]], [[4bu5\|4bu5]], [[4bu6\|4bu6]], [[4bu7\|4bu7]], [[4bu8\|4bu8]], [[4bu9\|4bu9]], [[4bua\|4bua]], [[4bud\|4bud]], [[4bue\|4bue]], [[4buf\|4buf]], [[4bui\|4bui]], [[4bus\|4bus]], [[4buu\|4buu]], [[4buv\|4buv]], [[4buw\|4buw]], [[4bux\|4bux]], [[4buy\|4buy]]</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=4but FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4but OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4but RCSB], [http://www.ebi.ac.uk/pdbsum/4but PDBsum]</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=4but FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4but OCA], [http://pdbe.org/4but PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4but RCSB], [http://www.ebi.ac.uk/pdbsum/4but PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4but ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4but" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 22:11, 25 December 2014

OCA — Thu, 25 Dec 2014 22:11:59 GMT

←Older revision		Revision as of 22:11, 25 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4but\| PDB=4but \| SCENE= }}~~	+	==Crystal structure of human tankyrase 2 in complex with 4-(4-oxo-3,4- dihydroquinazolin-2-yl)benzene-1-sulfonamide==
-	===Crystal structure of human tankyrase 2 in complex with 4-(4-oxo-3,4- dihydroquinazolin-2-yl)benzene-1-sulfonamide===	+	<StructureSection load='4but' size='340' side='right' caption='[[4but]], [[Resolution\|resolution]] 1.90Å' scene=''>
-	~~{{ABSTRACT_PUBMED_24130191}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4but]] 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=4BUT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BUT FirstGlance]. <br>
-	==Function==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=31F:4-(4-OXIDANYLIDENE-3H-QUINAZOLIN-2-YL)BENZENESULFONAMIDE'>31F</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4bu3\|4bu3]], [[4bu5\|4bu5]], [[4bu6\|4bu6]], [[4bu7\|4bu7]], [[4bu8\|4bu8]], [[4bu9\|4bu9]], [[4bua\|4bua]], [[4bud\|4bud]], [[4bue\|4bue]], [[4buf\|4buf]], [[4bui\|4bui]], [[4bus\|4bus]], [[4buu\|4buu]], [[4buv\|4buv]], [[4buw\|4buw]], [[4bux\|4bux]], [[4buy\|4buy]]</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=4but FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4but OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4but RCSB], [http://www.ebi.ac.uk/pdbsum/4but PDBsum]</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>		[[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 ==
		+	Human tankyrases are attractive drug targets, especially for the treatment of cancer. We identified a set of highly potent tankyrase inhibitors based on a 2-phenyl-3,4-dihydroquinazolin-4-one scaffold. Substitutions at the para position of the scaffold's phenyl group were evaluated as a strategy to increase potency and improve selectivity. The best compounds displayed single-digit nanomolar potencies, and profiling against several human diphtheria-toxin-like ADP-ribosyltransferases revealed that a subset of these compounds are highly selective tankyrase inhibitors. The compounds also effectively inhibit Wnt signaling in HEK293 cells. The binding mode of all inhibitors was studied by protein X-ray crystallography. This allowed us to establish a structural basis for the development of highly potent and selective tankyrase inhibitors based on the 2-phenyl-3,4-dihydroquinazolin-4-one scaffold and outline a rational approach to the modification of other inhibitor scaffolds that bind to the nicotinamide site of the catalytic domain.
		+
		+	para-Substituted 2-Phenyl-3,4-dihydroquinazolin-4-ones As Potent and Selective Tankyrase Inhibitors.,Haikarainen T, Koivunen J, Narwal M, Venkannagari H, Obaji E, Joensuu P, Pihlajaniemi T, Lehtio L ChemMedChem. 2013 Oct 15. doi: 10.1002/cmdc.201300337. PMID:24130191<ref>PMID:24130191</ref>

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4but]] 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=4BUT OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:024130191</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[Poly (ADP-ribose) polymerase\|Poly (ADP-ribose) polymerase]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Human]]		[[Category: Human]]
-	[[Category: Haikarainen, T.]]	+	[[Category: Haikarainen, T]]
-	[[Category: Lehtio, L.]]	+	[[Category: Lehtio, L]]
-	[[Category: Narwal, M.]]	+	[[Category: Narwal, M]]
	[[Category: Adp- ribosylation]]		[[Category: Adp- ribosylation]]
	[[Category: Diphtheria toxin like fold]]		[[Category: Diphtheria toxin like fold]]

OCA at 12:31, 11 December 2013

OCA — Wed, 11 Dec 2013 12:31:56 GMT

←Older revision		Revision as of 12:31, 11 December 2013
Line 7:		Line 7:

	==About this Structure==		==About this Structure==
-	[[4but]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BUT OCA].	+	[[4but]] 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=4BUT OCA].

	==Reference==		==Reference==
	<ref group="xtra">PMID:024130191</ref><references group="xtra"/><references/>		<ref group="xtra">PMID:024130191</ref><references group="xtra"/><references/>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Haikarainen, T.]]		[[Category: Haikarainen, T.]]
	[[Category: Lehtio, L.]]		[[Category: Lehtio, L.]]

OCA at 09:35, 30 October 2013

OCA — Wed, 30 Oct 2013 09:35:39 GMT

←Older revision		Revision as of 09:35, 30 October 2013
Line 1:		Line 1:
-	~~'''Unreleased~~ structure~~'''~~	+	{{STRUCTURE_4but\| PDB=4but \| SCENE= }}
		+	===Crystal structure of human tankyrase 2 in complex with 4-(4-oxo-3,4- dihydroquinazolin-2-yl)benzene-1-sulfonamide===
		+	{{ABSTRACT_PUBMED_24130191}}

-	~~The entry 4but is ON HOLD~~ ~~until Paper Publication~~	+	==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>

-	~~Authors~~: ~~Haikarainen, T~~.~~, Narwal, M~~.~~, Lehtio, L~~.	+	==About this Structure==
		+	[[4but]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BUT OCA].

-	~~Description~~: ~~Crystal structure of human tankyrase 2 in complex with 4-(4-oxo-3~~,4-~~dihydroquinazolin~~-2-~~yl)benzene-1-sulfonamide~~	+	==Reference==
		+	<ref group="xtra">PMID:024130191</ref><references group="xtra"/><references/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Haikarainen, T.]]
		+	[[Category: Lehtio, L.]]
		+	[[Category: Narwal, M.]]
		+	[[Category: Adp- ribosylation]]
		+	[[Category: Diphtheria toxin like fold]]
		+	[[Category: Protein-ligand complex]]
		+	[[Category: Transferase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA: Protected "4but" [edit=sysop:move=sysop]

OCA — Wed, 03 Jul 2013 12:53:04 GMT

Protected "4but" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:53, 3 July 2013