4buf - Revision history

OCA at 11:05, 9 May 2024

2024-05-09T11:05:36Z

← Older revision		Revision as of 11:05, 9 May 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4buf]] 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=4BUF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BUF FirstGlance]. <br>		<table><tr><td colspan='2'>[[4buf]] 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=4BUF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BUF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F36:2-(4-ACETYLPHENYL)-3,4-DIHYDROQUINAZOLIN-4-ONE'>F36</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]] 2.5Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F36:2-(4-ACETYLPHENYL)-3,4-DIHYDROQUINAZOLIN-4-ONE'>F36</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4buf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4buf OCA], [https://pdbe.org/4buf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4buf RCSB], [https://www.ebi.ac.uk/pdbsum/4buf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4buf 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=4buf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4buf OCA], [https://pdbe.org/4buf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4buf RCSB], [https://www.ebi.ac.uk/pdbsum/4buf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4buf 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 4buf" style="background-color:#fffaf0;"></div>

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

OCA at 17:08, 7 September 2022

2022-09-07T17:08:45Z

← Older revision		Revision as of 17:08, 7 September 2022
Line 3:		Line 3:
	<StructureSection load='4buf' size='340' side='right'caption='[[4buf]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='4buf' size='340' side='right'caption='[[4buf]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4buf]] 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=4BUF OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=4BUF FirstGlance]. <br>		<table><tr><td colspan='2'>[[4buf]] 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=4BUF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BUF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F36:2-(4-ACETYLPHENYL)-3,4-DIHYDROQUINAZOLIN-4-ONE'>F36</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" id="ligandDat"><scene name='pdbligand=F36:2-(4-ACETYLPHENYL)-3,4-DIHYDROQUINAZOLIN-4-ONE'>F36</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='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]], [[4bui\|4bui]], [[4bus\|4bus]], [[4but\|4but]], [[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=4buf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4buf OCA], [https://pdbe.org/4buf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4buf RCSB], [https://www.ebi.ac.uk/pdbsum/4buf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4buf 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=4buf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4buf OCA], [~~http~~://pdbe.org/4buf PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4buf RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4buf PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4buf 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 4buf" 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 08:15, 4 November 2020

2020-11-04T08:15:59Z

← Older revision		Revision as of 08:15, 4 November 2020
Line 1:		Line 1:

	==Crystal structure of human tankyrase 2 in complex with 2-(4- acetylphenyl)-3,4-dihydroquinazolin-4-one==		==Crystal structure of human tankyrase 2 in complex with 2-(4- acetylphenyl)-3,4-dihydroquinazolin-4-one==
	<StructureSection load='4buf' size='340' side='right' caption='[[4buf]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='4buf' size='340' side='right'caption='[[4buf]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4buf]] 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=4BUF OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4BUF FirstGlance]. <br>		<table><tr><td colspan='2'>[[4buf]] 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=4BUF OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=4BUF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=F36:2-(4-ACETYLPHENYL)-3,4-DIHYDROQUINAZOLIN-4-ONE'>F36</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" id="ligandDat"><scene name='pdbligand=F36:2-(4-ACETYLPHENYL)-3,4-DIHYDROQUINAZOLIN-4-ONE'>F36</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='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]], [[4bui\|4bui]], [[4bus\|4bus]], [[4but\|4but]], [[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]], [[4bui\|4bui]], [[4bus\|4bus]], [[4but\|4but]], [[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=4buf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4buf OCA], [http://pdbe.org/4buf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4buf RCSB], [http://www.ebi.ac.uk/pdbsum/4buf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4buf 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=4buf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4buf OCA], [http://pdbe.org/4buf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4buf RCSB], [http://www.ebi.ac.uk/pdbsum/4buf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4buf 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

2019-01-30T09:08:01Z

← Older revision		Revision as of 09:08, 30 January 2019
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 4buf" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4buf" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Poly (ADP-ribose) polymerase\|Poly (ADP-ribose) polymerase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:46, 16 November 2017

2017-11-16T07:46:13Z

← Older revision		Revision as of 07:46, 16 November 2017
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 4buf" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4buf" style="background-color:#fffaf0;"></div>

	~~==See Also==~~
	*[[Poly (ADP-ribose) polymerase\|Poly (ADP-ribose) polymerase]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:52, 5 August 2016

2016-08-05T07:52:58Z

← Older revision		Revision as of 07:52, 5 August 2016
Line 1:		Line 1:

	==Crystal structure of human tankyrase 2 in complex with 2-(4- acetylphenyl)-3,4-dihydroquinazolin-4-one==		==Crystal structure of human tankyrase 2 in complex with 2-(4- acetylphenyl)-3,4-dihydroquinazolin-4-one==
	<StructureSection load='4buf' size='340' side='right' caption='[[4buf]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='4buf' size='340' side='right' caption='[[4buf]], [[Resolution\|resolution]] 2.50Å' 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]], [[4bui\|4bui]], [[4bus\|4bus]], [[4but\|4but]], [[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]], [[4bui\|4bui]], [[4bus\|4bus]], [[4but\|4but]], [[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=4buf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4buf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4buf RCSB], [http://www.ebi.ac.uk/pdbsum/4buf 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=4buf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4buf OCA], [http://pdbe.org/4buf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4buf RCSB], [http://www.ebi.ac.uk/pdbsum/4buf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4buf 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 4buf" style="background-color:#fffaf0;"></div>

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

OCA at 17:03, 25 December 2014

2014-12-25T17:03:51Z

← Older revision		Revision as of 17:03, 25 December 2014
Line 1:		Line 1:
	~~{{STRUCTURE_4buf\| PDB=4buf \| SCENE= }}~~		==Crystal structure of human tankyrase 2 in complex with 2-(4- acetylphenyl)-3,4-dihydroquinazolin-4-one==
	===Crystal structure of human tankyrase 2 in complex with 2-(4- acetylphenyl)-3,4-dihydroquinazolin-4-one===		<StructureSection load='4buf' size='340' side='right' caption='[[4buf]], [[Resolution\|resolution]] 2.50Å' scene=''>
	~~{{ABSTRACT_PUBMED_24130191}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[4buf]] 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=4BUF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BUF FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=F36:2-(4-ACETYLPHENYL)-3,4-DIHYDROQUINAZOLIN-4-ONE'>F36</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='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]], [[4bui\|4bui]], [[4bus\|4bus]], [[4but\|4but]], [[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=4buf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4buf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4buf RCSB], [http://www.ebi.ac.uk/pdbsum/4buf 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>
			<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.

	~~==Function==~~		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>
	~~[[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>

	~~==About this Structure==~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[4buf]] 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=4BUF 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 12:38, 11 December 2013

2013-12-11T12:38:33Z

← Older revision		Revision as of 12:38, 11 December 2013
Line 7:		Line 7:

	==About this Structure==		==About this Structure==
	[[4buf]] 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=4BUF OCA].		[[4buf]] 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=4BUF 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 09:44, 30 October 2013

2013-10-30T09:44:25Z

← Older revision		Revision as of 09:44, 30 October 2013
Line 1:		Line 1:
	~~'''Unreleased~~ structure~~'''~~		{{STRUCTURE_4buf\| PDB=4buf \| SCENE= }}
			===Crystal structure of human tankyrase 2 in complex with 2-(4- acetylphenyl)-3,4-dihydroquinazolin-4-one===
			{{ABSTRACT_PUBMED_24130191}}

	~~The entry 4buf 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==
			[[4buf]] 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=4BUF OCA].

	~~Description~~: ~~Crystal structure of human tankyrase 2 in complex with 2-(4-acetylphenyl)-3~~,4-~~dihydroquinazolin~~-4-~~one~~		==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 at 12:52, 3 July 2013

2013-07-03T12:52:41Z

← Older revision		Revision as of 12:52, 3 July 2013
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 4buf is ON HOLD		The entry 4buf is ON HOLD until Paper Publication

	Authors: Haikarainen, T., Narwal, M., Lehtio, L.		Authors: Haikarainen, T., Narwal, M., Lehtio, L.

	Description: Crystal structure of human tankyrase 2 in complex with 2-(4-acetylphenyl)-3,4-dihydroquinazolin-4-one		Description: Crystal structure of human tankyrase 2 in complex with 2-(4-acetylphenyl)-3,4-dihydroquinazolin-4-one