4msg - Revision history

OCA at 12:28, 1 March 2024

2024-03-01T12:28:55Z

← Older revision		Revision as of 12:28, 1 March 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4msg]] 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=4MSG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MSG FirstGlance]. <br>		<table><tr><td colspan='2'>[[4msg]] 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=4MSG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MSG FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2C6:3-[(4-OXO-3,4-DIHYDROQUINAZOLIN-2-YL)SULFANYL]-N-[TRANS-4-(5-PHENYL-1,3,4-OXADIAZOL-2-YL)CYCLOHEXYL]PROPANAMIDE'>2C6</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2C6:3-[(4-OXO-3,4-DIHYDROQUINAZOLIN-2-YL)SULFANYL]-N-[TRANS-4-(5-PHENYL-1,3,4-OXADIAZOL-2-YL)CYCLOHEXYL]PROPANAMIDE'>2C6</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=4msg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4msg OCA], [https://pdbe.org/4msg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4msg RCSB], [https://www.ebi.ac.uk/pdbsum/4msg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4msg 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=4msg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4msg OCA], [https://pdbe.org/4msg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4msg RCSB], [https://www.ebi.ac.uk/pdbsum/4msg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4msg ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/TNKS1_HUMAN TNKS1_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 (PARsylation) 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 PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length. Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. May be involved in spindle pole assembly through PARsylation of NUMA1.<ref>PMID:10988299</ref> <ref>PMID:11739745</ref> <ref>PMID:16076287</ref> <ref>PMID:19759537</ref> <ref>PMID:21478859</ref> <ref>PMID:22864114</ref>		[https://www.uniprot.org/uniprot/TNKS1_HUMAN TNKS1_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 (PARsylation) 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 PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length. Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. May be involved in spindle pole assembly through PARsylation of NUMA1.<ref>PMID:10988299</ref> <ref>PMID:11739745</ref> <ref>PMID:16076287</ref> <ref>PMID:19759537</ref> <ref>PMID:21478859</ref> <ref>PMID:22864114</ref>
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Tankyrases (TNKS1 and TNKS2) are proteins in the poly ADP-ribose polymerase (PARP) family. They have been shown to directly bind to axin proteins, which negatively regulate the Wnt pathway by promoting beta-catenin degradation. Inhibition of tankyrases may offer a novel approach to the treatment of APC-mutant colorectal cancer. Hit compound 8 was identified as an inhibitor of tankyrases through a combination of substructure searching of the Amgen compound collection based on a minimal binding pharmacophore hypothesis and high-throughput screening. Herein we report the structure- and property-based optimization of compound 8 leading to the identification of more potent and selective tankyrase inhibitors 22 and 49 with improved pharmacokinetic properties in rodents, which are well suited as tool compounds for further in vivo validation studies.

	Development of Novel Dual Binders as Potent, Selective, and Orally Bioavailable Tankyrase Inhibitors.,Hua Z, Bregman H, Buchanan JL, Chakka N, Guzman-Perez A, Gunaydin H, Huang X, Gu Y, Berry V, Liu J, Teffera Y, Huang L, Egge B, Emkey R, Mullady EL, Schneider S, Andrews PS, Acquaviva L, Dovey J, Mishra A, Newcomb J, Saffran D, Serafino R, Strathdee CA, Turci SM, Stanton M, Wilson C, Dimauro EF J Med Chem. 2013 Dec 11. PMID:24294969<ref>PMID:24294969</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 4msg" style="background-color:#fffaf0;"></div>~~

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

OCA at 10:05, 28 December 2022

2022-12-28T10:05:22Z

← Older revision		Revision as of 10:05, 28 December 2022
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	==Crystal structure of tankyrase 1 with compound 22==		==Crystal structure of tankyrase 1 with compound 22==
	<StructureSection load='4msg' size='340' side='right' caption='[[4msg]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='4msg' size='340' side='right'caption='[[4msg]], [[Resolution\|resolution]] 1.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4msg]] 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=4MSG OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4MSG FirstGlance]. <br>		<table><tr><td colspan='2'>[[4msg]] 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=4MSG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MSG FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2C6:3-[(4-OXO-3,4-DIHYDROQUINAZOLIN-2-YL)SULFANYL]-N-[TRANS-4-(5-PHENYL-1,3,4-OXADIAZOL-2-YL)CYCLOHEXYL]PROPANAMIDE'>2C6</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=2C6:3-[(4-OXO-3,4-DIHYDROQUINAZOLIN-2-YL)SULFANYL]-N-[TRANS-4-(5-PHENYL-1,3,4-OXADIAZOL-2-YL)CYCLOHEXYL]PROPANAMIDE'>2C6</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">[[4i9i\|4i9i]], [[4msk\|4msk]]</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=4msg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4msg OCA], [https://pdbe.org/4msg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4msg RCSB], [https://www.ebi.ac.uk/pdbsum/4msg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4msg ProSAT]</span></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TNKS, PARP5A, PARPL, TIN1, TINF1, TNKS1 ([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='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=4msg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4msg OCA], [~~http~~://pdbe.org/4msg PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4msg RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4msg PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4msg ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[~~[http~~://www.uniprot.org/uniprot/TNKS1_HUMAN TNKS1_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 (PARsylation) 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 PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length. Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. May be involved in spindle pole assembly through PARsylation of NUMA1.<ref>PMID:10988299</ref> <ref>PMID:11739745</ref> <ref>PMID:16076287</ref> <ref>PMID:19759537</ref> <ref>PMID:21478859</ref> <ref>PMID:22864114</ref>		[https://www.uniprot.org/uniprot/TNKS1_HUMAN TNKS1_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 (PARsylation) 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 PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length. Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. May be involved in spindle pole assembly through PARsylation of NUMA1.<ref>PMID:10988299</ref> <ref>PMID:11739745</ref> <ref>PMID:16076287</ref> <ref>PMID:19759537</ref> <ref>PMID:21478859</ref> <ref>PMID:22864114</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 20:

	==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: ~~Huang, X~~]]		[[Category: Large Structures]]
	[[Category: ~~Inhibitor]]~~		[[Category: Huang X]]
	~~[[Category: Parp]]~~
	~~[[Category: Tankyrase]]~~
	~~[[Category: Transferase-transferase inhibitor complex~~]]

OCA at 21:01, 4 August 2016

2016-08-04T21:01:58Z

← Older revision		Revision as of 21:01, 4 August 2016
Line 1:		Line 1:

	==Crystal structure of tankyrase 1 with compound 22==		==Crystal structure of tankyrase 1 with compound 22==
	<StructureSection load='4msg' size='340' side='right' caption='[[4msg]], [[Resolution\|resolution]] 1.80Å' scene=''>		<StructureSection load='4msg' size='340' side='right' caption='[[4msg]], [[Resolution\|resolution]] 1.80Å' scene=''>
Line 7:		Line 8:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TNKS, PARP5A, PARPL, TIN1, TINF1, TNKS1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TNKS, PARP5A, PARPL, TIN1, TINF1, TNKS1 ([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=4msg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4msg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4msg RCSB], [http://www.ebi.ac.uk/pdbsum/4msg 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=4msg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4msg OCA], [http://pdbe.org/4msg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4msg RCSB], [http://www.ebi.ac.uk/pdbsum/4msg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4msg ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	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 4msg" style="background-color:#fffaf0;"></div>

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

OCA at 13:07, 25 December 2014

2014-12-25T13:07:55Z

← Older revision		Revision as of 13:07, 25 December 2014
Line 1:		Line 1:
	~~{{STRUCTURE_4msg\| PDB~~=4msg \| ~~SCENE~~= }}		==Crystal structure of tankyrase 1 with compound 22==
	===~~Crystal~~ structure ~~of tankyrase~~ 1 with ~~compound 22~~===		<StructureSection load='4msg' size='340' side='right' caption='[[4msg]], [[Resolution\|resolution]] 1.80Å' scene=''>
	~~{{ABSTRACT_PUBMED_24294969}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[4msg]] 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=4MSG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MSG FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2C6:3-[(4-OXO-3,4-DIHYDROQUINAZOLIN-2-YL)SULFANYL]-N-[TRANS-4-(5-PHENYL-1,3,4-OXADIAZOL-2-YL)CYCLOHEXYL]PROPANAMIDE'>2C6</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">[[4i9i\|4i9i]], [[4msk\|4msk]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TNKS, PARP5A, PARPL, TIN1, TINF1, TNKS1 ([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='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=4msg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4msg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4msg RCSB], [http://www.ebi.ac.uk/pdbsum/4msg PDBsum]</span></td></tr>
			</table>
			== Function ==
			[[http://www.uniprot.org/uniprot/TNKS1_HUMAN TNKS1_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 (PARsylation) 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 PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length. Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. May be involved in spindle pole assembly through PARsylation of NUMA1.<ref>PMID:10988299</ref> <ref>PMID:11739745</ref> <ref>PMID:16076287</ref> <ref>PMID:19759537</ref> <ref>PMID:21478859</ref> <ref>PMID:22864114</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Tankyrases (TNKS1 and TNKS2) are proteins in the poly ADP-ribose polymerase (PARP) family. They have been shown to directly bind to axin proteins, which negatively regulate the Wnt pathway by promoting beta-catenin degradation. Inhibition of tankyrases may offer a novel approach to the treatment of APC-mutant colorectal cancer. Hit compound 8 was identified as an inhibitor of tankyrases through a combination of substructure searching of the Amgen compound collection based on a minimal binding pharmacophore hypothesis and high-throughput screening. Herein we report the structure- and property-based optimization of compound 8 leading to the identification of more potent and selective tankyrase inhibitors 22 and 49 with improved pharmacokinetic properties in rodents, which are well suited as tool compounds for further in vivo validation studies.

	~~==Function==~~		Development of Novel Dual Binders as Potent, Selective, and Orally Bioavailable Tankyrase Inhibitors.,Hua Z, Bregman H, Buchanan JL, Chakka N, Guzman-Perez A, Gunaydin H, Huang X, Gu Y, Berry V, Liu J, Teffera Y, Huang L, Egge B, Emkey R, Mullady EL, Schneider S, Andrews PS, Acquaviva L, Dovey J, Mishra A, Newcomb J, Saffran D, Serafino R, Strathdee CA, Turci SM, Stanton M, Wilson C, Dimauro EF J Med Chem. 2013 Dec 11. PMID:24294969<ref>PMID:24294969</ref>
	~~[[http://www.uniprot.org/uniprot/TNKS1_HUMAN TNKS1_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 (PARsylation) 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 PARsylation of BLZF1 and CASC3~~, ~~followed by recruitment of RNF146 and subsequent ubiquitination. Mediates PARsylation of TERF1~~, thereby contributing to the regulation of telomere length. Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. ~~May be involved in spindle pole assembly through PARsylation of NUMA1~~.~~<ref>~~PMID:~~10988299</ref> <ref>PMID:11739745</ref> <ref>PMID:16076287</ref> <ref>PMID:19759537</ref> <ref>PMID:21478859</ref>~~ <ref>PMID:~~22864114~~</ref>

	~~==About this Structure==~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[4msg]] is~~ a ~~2 chain structure. Full crystallographic information is available from [http://oca~~.~~weizmann~~.ac.~~il/oca-bin~~/~~ocashort?id=4MSG OCA].~~		</div>

	==~~Reference~~==		==See Also==
	~~<ref group~~=~~"xtra">PMID:024294969</ref>~~<references ~~group="xtra"~~/><~~references~~/>		*[[Poly (ADP-ribose) polymerase\|Poly (ADP-ribose) polymerase]]
	[[Category: Huang, X.]]		== References ==
			<references/>
			__TOC__
			</StructureSection>
			[[Category: Human]]
			[[Category: Huang, X]]
	[[Category: Inhibitor]]		[[Category: Inhibitor]]
	[[Category: Parp]]		[[Category: Parp]]
	[[Category: Tankyrase]]		[[Category: Tankyrase]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 10:17, 25 December 2013

2013-12-25T10:17:57Z

← Older revision		Revision as of 10:17, 25 December 2013
Line 1:		Line 1:
	~~'''Unreleased~~ structure~~'''~~		{{STRUCTURE_4msg\| PDB=4msg \| SCENE= }}
			===Crystal structure of tankyrase 1 with compound 22===
			{{ABSTRACT_PUBMED_24294969}}

	~~The entry 4msg is ON HOLD~~		==Function==
			[[http://www.uniprot.org/uniprot/TNKS1_HUMAN TNKS1_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 (PARsylation) 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 PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length. Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. May be involved in spindle pole assembly through PARsylation of NUMA1.<ref>PMID:10988299</ref> <ref>PMID:11739745</ref> <ref>PMID:16076287</ref> <ref>PMID:19759537</ref> <ref>PMID:21478859</ref> <ref>PMID:22864114</ref>

	~~Authors~~: ~~Huang, X~~.		==About this Structure==
			[[4msg]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MSG OCA].

	~~Description~~: ~~Crystal structure of tankyrase 1 with compound 22~~		==Reference==
			<ref group="xtra">PMID:024294969</ref><references group="xtra"/><references/>
			[[Category: Huang, X.]]
			[[Category: Inhibitor]]
			[[Category: Parp]]
			[[Category: Tankyrase]]
			[[Category: Transferase-transferase inhibitor complex]]

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

2013-09-29T07:43:50Z

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

← Older revision	Revision as of 07:43, 29 September 2013
(No difference)

OCA: New page: '''Unreleased structure''' The entry 4msg is ON HOLD Authors: Huang, X. Description: Crystal structure of tankyrase 1 with compound 22

2013-09-29T07:43:50Z

New page: '''Unreleased structure''' The entry 4msg is ON HOLD Authors: Huang, X. Description: Crystal structure of tankyrase 1 with compound 22

New page

'''Unreleased structure'''

The entry 4msg is ON HOLD

Authors: Huang, X.

Description: Crystal structure of tankyrase 1 with compound 22