4k4e - Revision history

OCA at 12:08, 1 March 2024

2024-03-01T12:08:29Z

← Older revision		Revision as of 12:08, 1 March 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4k4e]] 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=4K4E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4K4E FirstGlance]. <br>		<table><tr><td colspan='2'>[[4k4e]] 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=4K4E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4K4E FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K4E:N~2~-(5-CHLORO-2-METHOXYPHENYL)-N-[TRANS-4-(2-OXO-2,3-DIHYDRO-1H-BENZIMIDAZOL-1-YL)CYCLOHEXYL]GLYCINAMIDE'>K4E</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]] 2.3Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K4E:N~2~-(5-CHLORO-2-METHOXYPHENYL)-N-[TRANS-4-(2-OXO-2,3-DIHYDRO-1H-BENZIMIDAZOL-1-YL)CYCLOHEXYL]GLYCINAMIDE'>K4E</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=4k4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k4e OCA], [https://pdbe.org/4k4e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4k4e RCSB], [https://www.ebi.ac.uk/pdbsum/4k4e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4k4e 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=4k4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k4e OCA], [https://pdbe.org/4k4e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4k4e RCSB], [https://www.ebi.ac.uk/pdbsum/4k4e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4k4e 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 ==~~
	Tankyrase (TNKS) is a poly-ADP-ribosylating protein (PARP) whose activity suppresses cellular axin protein levels and elevates beta-catenin concentrations, resulting in increased oncogene expression. The inhibition of tankyrase (TNKS1 and 2) may reduce the levels of beta-catenin-mediated transcription and inhibit tumorigenesis. Compound 1 is a previously described moderately potent tankyrase inhibitor that suffers from poor pharmacokinetic properties. Herein, we describe the utilization of structure-based design and molecular modeling toward novel, potent, and selective tankyrase inhibitors with improved pharmacokinetic properties (39, 40).

	Discovery of Novel, Induced-Pocket Binding Oxazolidinones as Potent, Selective, and Orally Bioavailable Tankyrase Inhibitors.,Bregman H, Chakka N, Guzman-Perez A, Gunaydin H, Gu Y, Huang X, Berry V, Liu J, Teffera Y, Huang L, Egge B, Mullady EL, Schneider S, Andrews PS, Mishra A, Newcomb J, Serafino R, Strathdee CA, Turci SM, Wilson C, Dimauro EF J Med Chem. 2013 May 23. PMID:23701517<ref>PMID:23701517</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 4k4e" style="background-color:#fffaf0;"></div>~~

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

OCA at 11:39, 30 November 2022

2022-11-30T11:39:42Z

← Older revision		Revision as of 11:39, 30 November 2022
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	==Co-crystal structure of tnks1 with compound 52 [N~2-(5-chloro-2-methoxyphenyl)-N-[trans-4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)cyclohexyl]glycinamide]==		==Co-crystal structure of tnks1 with compound 52 [N~2-(5-chloro-2-methoxyphenyl)-N-[trans-4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)cyclohexyl]glycinamide]==
	<StructureSection load='4k4e' size='340' side='right' caption='[[4k4e]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='4k4e' size='340' side='right'caption='[[4k4e]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4k4e]] 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=4K4E OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4K4E FirstGlance]. <br>		<table><tr><td colspan='2'>[[4k4e]] 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=4K4E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4K4E FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K4E:N~2~-(5-CHLORO-2-METHOXYPHENYL)-N-[TRANS-4-(2-OXO-2,3-DIHYDRO-1H-BENZIMIDAZOL-1-YL)CYCLOHEXYL]GLYCINAMIDE'>K4E</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=K4E:N~2~-(5-CHLORO-2-METHOXYPHENYL)-N-[TRANS-4-(2-OXO-2,3-DIHYDRO-1H-BENZIMIDAZOL-1-YL)CYCLOHEXYL]GLYCINAMIDE'>K4E</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">[[4dvi\|4dvi]], [[4k4f\|4k4f]]</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=4k4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k4e OCA], [https://pdbe.org/4k4e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4k4e RCSB], [https://www.ebi.ac.uk/pdbsum/4k4e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4k4e 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=4k4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k4e OCA], [~~http~~://pdbe.org/4k4e PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4k4e RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4k4e PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4k4e 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: ~~Parp]]~~		[[Category: Huang X]]
	~~[[Category: Transferase-transferase inhibitor complex~~]]

OCA at 07:04, 5 August 2016

2016-08-05T07:04:37Z

← Older revision		Revision as of 07:04, 5 August 2016
Line 1:		Line 1:

	==Co-crystal structure of tnks1 with compound 52 [N~2-(5-chloro-2-methoxyphenyl)-N-[trans-4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)cyclohexyl]glycinamide]==		==Co-crystal structure of tnks1 with compound 52 [N~2-(5-chloro-2-methoxyphenyl)-N-[trans-4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)cyclohexyl]glycinamide]==
	<StructureSection load='4k4e' size='340' side='right' caption='[[4k4e]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='4k4e' size='340' side='right' caption='[[4k4e]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4k4e]] 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=4K4E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K4E FirstGlance]. <br>		<table><tr><td colspan='2'>[[4k4e]] 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=4K4E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K4E FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K4E:N~2~-(5-CHLORO-2-METHOXYPHENYL)-N-[TRANS-4-(2-OXO-2,3-DIHYDRO-1H-BENZIMIDAZOL-1-YL)CYCLOHEXYL]GLYCINAMIDE'>K4E</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K4E:N~2~-(5-CHLORO-2-METHOXYPHENYL)-N-[TRANS-4-(2-OXO-2,3-DIHYDRO-1H-BENZIMIDAZOL-1-YL)CYCLOHEXYL]GLYCINAMIDE'>K4E</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">[[4dvi\|4dvi]], [[4k4f\|4k4f]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4dvi\|4dvi]], [[4k4f\|4k4f]]</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 ~~Homo sapiens~~])</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=4k4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k4e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4k4e RCSB], [http://www.ebi.ac.uk/pdbsum/4k4e 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=4k4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k4e OCA], [http://pdbe.org/4k4e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4k4e RCSB], [http://www.ebi.ac.uk/pdbsum/4k4e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4k4e 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 4k4e" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 26:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Huang, X]]		[[Category: Huang, X]]
	[[Category: Parp]]		[[Category: Parp]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 00:05, 25 December 2014

2014-12-25T00:05:01Z

← Older revision		Revision as of 00:05, 25 December 2014
Line 9:		Line 9:
	<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=4k4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k4e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4k4e RCSB], [http://www.ebi.ac.uk/pdbsum/4k4e 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=4k4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k4e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4k4e RCSB], [http://www.ebi.ac.uk/pdbsum/4k4e PDBsum]</span></td></tr>
	</table>		</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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 15:16, 21 December 2014

2014-12-21T15:16:14Z

← Older revision		Revision as of 15:16, 21 December 2014
Line 1:		Line 1:
	~~{{STRUCTURE_4k4e\| PDB=4k4e \| SCENE= }}~~		==Co-crystal structure of tnks1 with compound 52 [N~2-(5-chloro-2-methoxyphenyl)-N-[trans-4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)cyclohexyl]glycinamide]==
	===Co-crystal structure of tnks1 with compound 52 [N~2-(5-chloro-2-methoxyphenyl)-N-[trans-4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)cyclohexyl]glycinamide]===		<StructureSection load='4k4e' size='340' side='right' caption='[[4k4e]], [[Resolution\|resolution]] 2.30Å' scene=''>
	~~{{ABSTRACT_PUBMED_23701517}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[4k4e]] 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=4K4E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K4E FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K4E:N~2~-(5-CHLORO-2-METHOXYPHENYL)-N-[TRANS-4-(2-OXO-2,3-DIHYDRO-1H-BENZIMIDAZOL-1-YL)CYCLOHEXYL]GLYCINAMIDE'>K4E</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">[[4dvi\|4dvi]], [[4k4f\|4k4f]]</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 Homo sapiens])</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=4k4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k4e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4k4e RCSB], [http://www.ebi.ac.uk/pdbsum/4k4e PDBsum]</span></td></tr>
			</table>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Tankyrase (TNKS) is a poly-ADP-ribosylating protein (PARP) whose activity suppresses cellular axin protein levels and elevates beta-catenin concentrations, resulting in increased oncogene expression. The inhibition of tankyrase (TNKS1 and 2) may reduce the levels of beta-catenin-mediated transcription and inhibit tumorigenesis. Compound 1 is a previously described moderately potent tankyrase inhibitor that suffers from poor pharmacokinetic properties. Herein, we describe the utilization of structure-based design and molecular modeling toward novel, potent, and selective tankyrase inhibitors with improved pharmacokinetic properties (39, 40).

	~~==Function==~~		Discovery of Novel, Induced-Pocket Binding Oxazolidinones as Potent, Selective, and Orally Bioavailable Tankyrase Inhibitors.,Bregman H, Chakka N, Guzman-Perez A, Gunaydin H, Gu Y, Huang X, Berry V, Liu J, Teffera Y, Huang L, Egge B, Mullady EL, Schneider S, Andrews PS, Mishra A, Newcomb J, Serafino R, Strathdee CA, Turci SM, Wilson C, Dimauro EF J Med Chem. 2013 May 23. PMID:23701517<ref>PMID:23701517</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>
	~~[[4k4e]] 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=4K4E OCA].~~		</div>

	==~~Reference~~==		==See Also==
	~~<ref group~~=~~"xtra">PMID:023701517</ref>~~<references ~~group="xtra"~~/><~~references~~/>		*[[Poly (ADP-ribose) polymerase\|Poly (ADP-ribose) polymerase]]
			== References ==
			<references/>
			__TOC__
			</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Huang, X.]]		[[Category: Huang, X]]
	[[Category: Parp]]		[[Category: Parp]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 15:33, 19 June 2013

2013-06-19T15:33:14Z

← Older revision		Revision as of 15:33, 19 June 2013
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	~~'''Unreleased~~ structure~~'''~~		{{STRUCTURE_4k4e\| PDB=4k4e \| SCENE= }}
			===Co-crystal structure of tnks1 with compound 52 [N~2-(5-chloro-2-methoxyphenyl)-N-[trans-4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)cyclohexyl]glycinamide]===
			{{ABSTRACT_PUBMED_23701517}}

	~~The entry 4k4e is ON HOLD~~ ~~until Paper Publication~~		==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==
			[[4k4e]] 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=4K4E OCA].

	~~Description~~: ~~Co-crystal structure of tnks1 with compound 52~~ [~~N~2-(5-chloro-2-methoxyphenyl)-N-~~[~~trans-4-(2-oxo-2~~,~~3-dihydro-1H-benzimidazol-1~~-~~yl)cyclohexyl~~]~~glycinamide~~]		==Reference==
			<ref group="xtra">PMID:023701517</ref><references group="xtra"/><references/>
			[[Category: Homo sapiens]]
			[[Category: Huang, X.]]
			[[Category: Parp]]
			[[Category: Transferase-transferase inhibitor complex]]

OCA at 07:11, 2 May 2013

2013-05-02T07:11:28Z

← Older revision		Revision as of 07:11, 2 May 2013
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 4k4e is ON HOLD		The entry 4k4e is ON HOLD until Paper Publication

	Authors: Huang, X.		Authors: Huang, X.

	Description: co-crystal structure of tnks1 with compound 52		Description: Co-crystal structure of tnks1 with compound 52 [N~2-(5-chloro-2-methoxyphenyl)-N-[trans-4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)cyclohexyl]glycinamide]

OCA: Protected "4k4e" [edit=sysop:move=sysop]

2013-04-24T10:58:45Z

Protected "4k4e" [edit=sysop:move=sysop]

← Older revision	Revision as of 10:58, 24 April 2013
(No difference)

OCA: New page: '''Unreleased structure''' The entry 4k4e is ON HOLD Authors: Huang, X. Description: co-crystal structure of tnks1 with compound 52

2013-04-24T10:58:44Z

New page: '''Unreleased structure''' The entry 4k4e is ON HOLD Authors: Huang, X. Description: co-crystal structure of tnks1 with compound 52

New page

'''Unreleased structure'''

The entry 4k4e is ON HOLD

Authors: Huang, X.

Description: co-crystal structure of tnks1 with compound 52