4r5w - Revision history

OCA at 17:44, 20 September 2023

OCA — Wed, 20 Sep 2023 17:44:37 GMT

←Older revision		Revision as of 17:44, 20 September 2023
Line 1:		Line 1:

	==Human artd1 (parp1) - catalytic domain in complex with inhibitor xav939==		==Human artd1 (parp1) - catalytic domain in complex with inhibitor xav939==
-	<StructureSection load='4r5w' size='340' side='right'caption='[[4r5w]]' scene=''>	+	<StructureSection load='4r5w' size='340' side='right'caption='[[4r5w]], [[Resolution\|resolution]] 2.84Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R5W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R5W FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4r5w]] 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=4R5W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R5W FirstGlance]. <br>
-	</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=4r5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r5w OCA], [https://pdbe.org/4r5w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r5w RCSB], [https://www.ebi.ac.uk/pdbsum/4r5w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r5w ProSAT]</span></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]] 2.84Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=XAV:2-[4-(TRIFLUOROMETHYL)PHENYL]-7,8-DIHYDRO-5H-THIOPYRANO[4,3-D]PYRIMIDIN-4-OL'>XAV</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=4r5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r5w OCA], [https://pdbe.org/4r5w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r5w RCSB], [https://www.ebi.ac.uk/pdbsum/4r5w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r5w ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/PARP1_HUMAN PARP1_HUMAN] Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. Mediates the poly(ADP-ribosyl)ation of APLF and CHFR. Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production.<ref>PMID:17177976</ref> <ref>PMID:18172500</ref> <ref>PMID:19344625</ref> <ref>PMID:19661379</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Selective inhibitors could help unveil the mechanisms by which inhibition of poly(ADP-ribose) polymerases (PARPs) elicits clinical benefits in cancer therapy. We profiled 10 clinical PARP inhibitors and commonly used research tools for their inhibition of multiple PARP enzymes. We also determined crystal structures of these compounds bound to PARP1 or PARP2. Veliparib and niraparib are selective inhibitors of PARP1 and PARP2; olaparib, rucaparib, and talazoparib are more potent inhibitors of PARP1 but are less selective. PJ34 and UPF1069 are broad PARP inhibitors; PJ34 inserts a flexible moiety into hydrophobic subpockets in various ADP-ribosyltransferases. XAV939 is a promiscuous tankyrase inhibitor and a potent inhibitor of PARP1 in vitro and in cells, whereas IWR1 and AZ-6102 are tankyrase selective. Our biochemical and structural analysis of PARP inhibitor potencies establishes a molecular basis for either selectivity or promiscuity and provides a benchmark for experimental design in assessment of PARP inhibitor effects.
		+
		+	Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors.,Thorsell AG, Ekblad T, Karlberg T, Low M, Pinto AF, Tresaugues L, Moche M, Cohen MS, Schuler H J Med Chem. 2016 Dec 21. PMID:28001384<ref>PMID:28001384</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 4r5w" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Poly(ADP-ribose) polymerase 3D structures\|Poly(ADP-ribose) polymerase 3D structures]]		*[[Poly(ADP-ribose) polymerase 3D structures\|Poly(ADP-ribose) polymerase 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Karlberg T]]		[[Category: Karlberg T]]
	[[Category: Schuler H]]		[[Category: Schuler H]]
	[[Category: Thorsell AG]]		[[Category: Thorsell AG]]

OCA at 10:57, 31 August 2022

OCA — Wed, 31 Aug 2022 10:57:41 GMT

←Older revision		Revision as of 10:57, 31 August 2022
Line 1:		Line 1:

	==Human artd1 (parp1) - catalytic domain in complex with inhibitor xav939==		==Human artd1 (parp1) - catalytic domain in complex with inhibitor xav939==
-	<StructureSection load='4r5w' size='340' side='right'caption='[[4r5w]]~~, [[Resolution\|resolution]] 2.84Å~~' scene=''>	+	<StructureSection load='4r5w' size='340' side='right'caption='[[4r5w]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>~~[[4r5w]] is a 2 chain structure.~~ Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R5W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R5W FirstGlance]. <br>	+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R5W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R5W FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=XAV:2-[4-(TRIFLUOROMETHYL)PHENYL]-7,8-DIHYDRO-5H-THIOPYRANO[4,3-D]PYRIMIDIN-4-OL'>XAV</scene></td></tr>	+	</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=4r5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r5w OCA], [https://pdbe.org/4r5w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r5w RCSB], [https://www.ebi.ac.uk/pdbsum/4r5w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r5w ProSAT]</span></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[4und\|4und]], [[4uxb\|4uxb]], [[4r6e\|4r6e]]</div></td></tr>	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </span></td></tr>	+
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4r5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r5w OCA], [https://pdbe.org/4r5w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r5w RCSB], [https://www.ebi.ac.uk/pdbsum/4r5w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r5w ProSAT]</span></td></tr>	+
	</table>		</table>
-	== Function ==
-	[[https://www.uniprot.org/uniprot/PARP1_HUMAN PARP1_HUMAN]] Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. Mediates the poly(ADP-ribosyl)ation of APLF and CHFR. Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production.<ref>PMID:17177976</ref> <ref>PMID:18172500</ref> <ref>PMID:19344625</ref> <ref>PMID:19661379</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Selective inhibitors could help unveil the mechanisms by which inhibition of poly(ADP-ribose) polymerases (PARPs) elicits clinical benefits in cancer therapy. We profiled 10 clinical PARP inhibitors and commonly used research tools for their inhibition of multiple PARP enzymes. We also determined crystal structures of these compounds bound to PARP1 or PARP2. Veliparib and niraparib are selective inhibitors of PARP1 and PARP2; olaparib, rucaparib, and talazoparib are more potent inhibitors of PARP1 but are less selective. PJ34 and UPF1069 are broad PARP inhibitors; PJ34 inserts a flexible moiety into hydrophobic subpockets in various ADP-ribosyltransferases. XAV939 is a promiscuous tankyrase inhibitor and a potent inhibitor of PARP1 in vitro and in cells, whereas IWR1 and AZ-6102 are tankyrase selective. Our biochemical and structural analysis of PARP inhibitor potencies establishes a molecular basis for either selectivity or promiscuity and provides a benchmark for experimental design in assessment of PARP inhibitor effects.
-
-	Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors.,Thorsell AG, Ekblad T, Karlberg T, Low M, Pinto AF, Tresaugues L, Moche M, Cohen MS, Schuler H J Med Chem. 2016 Dec 21. PMID:28001384<ref>PMID:28001384</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4r5w" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Poly(ADP-ribose) polymerase 3D structures\|Poly(ADP-ribose) polymerase 3D structures]]		*[[Poly(ADP-ribose) polymerase 3D structures\|Poly(ADP-ribose) polymerase 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Karlberg, T]]	+	[[Category: Karlberg T]]
-	[[Category: Schuler, H]]	+	[[Category: Schuler H]]
-	[[Category: Thorsell~~, A G]]~~	+	[[Category: Thorsell AG]]
-	~~[[Category: Adp-ribosyl transferase]]~~	+
-	~~[[Category: Adp-ribosylation]]~~	+
-	~~[[Category: Dna repair]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 05:08, 25 August 2022

OCA — Thu, 25 Aug 2022 05:08:13 GMT

←Older revision		Revision as of 05:08, 25 August 2022
Line 1:		Line 1:

	==Human artd1 (parp1) - catalytic domain in complex with inhibitor xav939==		==Human artd1 (parp1) - catalytic domain in complex with inhibitor xav939==
-	<StructureSection load='4r5w' size='340' side='right' caption='[[4r5w]], [[Resolution\|resolution]] 2.84Å' scene=''>	+	<StructureSection load='4r5w' size='340' side='right'caption='[[4r5w]], [[Resolution\|resolution]] 2.84Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4r5w]] 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=4R5W OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4R5W FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4r5w]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R5W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R5W FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=XAV:2-[4-(TRIFLUOROMETHYL)PHENYL]-7,8-DIHYDRO-5H-THIOPYRANO[4,3-D]PYRIMIDIN-4-OL'>XAV</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=XAV:2-[4-(TRIFLUOROMETHYL)PHENYL]-7,8-DIHYDRO-5H-THIOPYRANO[4,3-D]PYRIMIDIN-4-OL'>XAV</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4und\|4und]], [[4uxb\|4uxb]], [[4r6e\|4r6e]]</td>~~</tr>~~	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[4und\|4und]], [[4uxb\|4uxb]], [[4r6e\|4r6e]]</div></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ADPRT, PARP1, PPOL ([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'>[https://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=4r5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r5w OCA], [https://pdbe.org/4r5w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r5w RCSB], [https://www.ebi.ac.uk/pdbsum/4r5w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r5w ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4r5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r5w OCA], [~~http~~://pdbe.org/4r5w PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4r5w RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4r5w PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4r5w ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/PARP1_HUMAN PARP1_HUMAN]] Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. Mediates the poly(ADP-ribosyl)ation of APLF and CHFR. Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production.<ref>PMID:17177976</ref> <ref>PMID:18172500</ref> <ref>PMID:19344625</ref> <ref>PMID:19661379</ref>	+	[[https://www.uniprot.org/uniprot/PARP1_HUMAN PARP1_HUMAN]] Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. Mediates the poly(ADP-ribosyl)ation of APLF and CHFR. Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production.<ref>PMID:17177976</ref> <ref>PMID:18172500</ref> <ref>PMID:19344625</ref> <ref>PMID:19661379</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 4r5w" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4r5w" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Poly(ADP-ribose) polymerase 3D structures\|Poly(ADP-ribose) polymerase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Large Structures]]
	[[Category: Karlberg, T]]		[[Category: Karlberg, T]]
	[[Category: Schuler, H]]		[[Category: Schuler, H]]

OCA at 09:01, 22 November 2017

OCA — Wed, 22 Nov 2017 09:01:45 GMT

←Older revision		Revision as of 09:01, 22 November 2017
Line 3:		Line 3:
	<StructureSection load='4r5w' size='340' side='right' caption='[[4r5w]], [[Resolution\|resolution]] 2.84Å' scene=''>		<StructureSection load='4r5w' size='340' side='right' caption='[[4r5w]], [[Resolution\|resolution]] 2.84Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4r5w]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R5W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R5W FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4r5w]] 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=4R5W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R5W FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=XAV:2-[4-(TRIFLUOROMETHYL)PHENYL]-7,8-DIHYDRO-5H-THIOPYRANO[4,3-D]PYRIMIDIN-4-OL'>XAV</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=XAV:2-[4-(TRIFLUOROMETHYL)PHENYL]-7,8-DIHYDRO-5H-THIOPYRANO[4,3-D]PYRIMIDIN-4-OL'>XAV</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4und\|4und]], [[4uxb\|4uxb]], [[4r6e\|4r6e]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4und\|4und]], [[4uxb\|4uxb]], [[4r6e\|4r6e]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ADPRT, PARP1, PPOL ([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=4r5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r5w OCA], [http://pdbe.org/4r5w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4r5w RCSB], [http://www.ebi.ac.uk/pdbsum/4r5w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4r5w ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4r5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r5w OCA], [http://pdbe.org/4r5w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4r5w RCSB], [http://www.ebi.ac.uk/pdbsum/4r5w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4r5w ProSAT]</span></td></tr>
Line 24:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Karlberg, T]]		[[Category: Karlberg, T]]
	[[Category: Schuler, H]]		[[Category: Schuler, H]]

OCA at 07:37, 18 January 2017

OCA — Wed, 18 Jan 2017 07:37:19 GMT

←Older revision		Revision as of 07:37, 18 January 2017
Line 1:		Line 1:
		+
	==Human artd1 (parp1) - catalytic domain in complex with inhibitor xav939==		==Human artd1 (parp1) - catalytic domain in complex with inhibitor xav939==
	<StructureSection load='4r5w' size='340' side='right' caption='[[4r5w]], [[Resolution\|resolution]] 2.84Å' scene=''>		<StructureSection load='4r5w' size='340' side='right' caption='[[4r5w]], [[Resolution\|resolution]] 2.84Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4und\|4und]], [[4uxb\|4uxb]], [[4r6e\|4r6e]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4und\|4und]], [[4uxb\|4uxb]], [[4r6e\|4r6e]]</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=4r5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r5w OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4r5w RCSB], [http://www.ebi.ac.uk/pdbsum/4r5w 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=4r5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r5w OCA], [http://pdbe.org/4r5w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4r5w RCSB], [http://www.ebi.ac.uk/pdbsum/4r5w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4r5w ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/PARP1_HUMAN PARP1_HUMAN]] Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. Mediates the poly(ADP-ribosyl)ation of APLF and CHFR. Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production.<ref>PMID:17177976</ref> <ref>PMID:18172500</ref> <ref>PMID:19344625</ref> <ref>PMID:19661379</ref>		[[http://www.uniprot.org/uniprot/PARP1_HUMAN PARP1_HUMAN]] Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. Mediates the poly(ADP-ribosyl)ation of APLF and CHFR. Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production.<ref>PMID:17177976</ref> <ref>PMID:18172500</ref> <ref>PMID:19344625</ref> <ref>PMID:19661379</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Selective inhibitors could help unveil the mechanisms by which inhibition of poly(ADP-ribose) polymerases (PARPs) elicits clinical benefits in cancer therapy. We profiled 10 clinical PARP inhibitors and commonly used research tools for their inhibition of multiple PARP enzymes. We also determined crystal structures of these compounds bound to PARP1 or PARP2. Veliparib and niraparib are selective inhibitors of PARP1 and PARP2; olaparib, rucaparib, and talazoparib are more potent inhibitors of PARP1 but are less selective. PJ34 and UPF1069 are broad PARP inhibitors; PJ34 inserts a flexible moiety into hydrophobic subpockets in various ADP-ribosyltransferases. XAV939 is a promiscuous tankyrase inhibitor and a potent inhibitor of PARP1 in vitro and in cells, whereas IWR1 and AZ-6102 are tankyrase selective. Our biochemical and structural analysis of PARP inhibitor potencies establishes a molecular basis for either selectivity or promiscuity and provides a benchmark for experimental design in assessment of PARP inhibitor effects.
		+
		+	Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors.,Thorsell AG, Ekblad T, Karlberg T, Low M, Pinto AF, Tresaugues L, Moche M, Cohen MS, Schuler H J Med Chem. 2016 Dec 21. PMID:28001384<ref>PMID:28001384</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 4r5w" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 12:28, 2 September 2015

OCA — Wed, 02 Sep 2015 12:28:57 GMT

←Older revision		Revision as of 12:28, 2 September 2015
Line 1:		Line 1:
-	'''~~Unreleased structure~~'''	+	==Human artd1 (parp1) - catalytic domain in complex with inhibitor xav939==
-		+	<StructureSection load='4r5w' size='340' side='right' caption='[[4r5w]], [[Resolution\|resolution]] 2.84Å' scene=''>
-	~~The entry~~ 4r5w is ~~ON HOLD until Paper Publication~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4r5w]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R5W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4R5W FirstGlance]. <br>
-	~~Authors~~: ~~Karlberg, T~~.~~, Thorsell, A~~.G.~~, Schuler, H~~.	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=XAV:2-[4-(TRIFLUOROMETHYL)PHENYL]-7,8-DIHYDRO-5H-THIOPYRANO[4,3-D]PYRIMIDIN-4-OL'>XAV</scene></td></tr>
-		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4und\|4und]], [[4uxb\|4uxb]], [[4r6e\|4r6e]]</td></tr>
-	~~Description~~: ~~Human artd1~~ (~~parp1~~) -~~catalytic domain in complex with inhibitor xav939~~	+	<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>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	<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=4r5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r5w OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4r5w RCSB], [http://www.ebi.ac.uk/pdbsum/4r5w PDBsum]</span></td></tr>
-	[[~~Category~~: ~~Thorsell~~, A.G]]	+	</table>
-	[[~~Category~~: ~~Schuler, H~~]]	+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PARP1_HUMAN PARP1_HUMAN]] Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. Mediates the poly(ADP-ribosyl)ation of APLF and CHFR. Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production.<ref>PMID:17177976</ref> <ref>PMID:18172500</ref> <ref>PMID:19344625</ref> <ref>PMID:19661379</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Karlberg, T]]		[[Category: Karlberg, T]]
		+	[[Category: Schuler, H]]
		+	[[Category: Thorsell, A G]]
		+	[[Category: Adp-ribosyl transferase]]
		+	[[Category: Adp-ribosylation]]
		+	[[Category: Dna repair]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA at 16:31, 24 December 2014

OCA — Wed, 24 Dec 2014 16:31:05 GMT

←Older revision		Revision as of 16:31, 24 December 2014
Line 6:		Line 6:

	Description: Human artd1 (parp1) -catalytic domain in complex with inhibitor xav939		Description: Human artd1 (parp1) -catalytic domain in complex with inhibitor xav939
		+	[[Category: Unreleased Structures]]
		+	[[Category: Thorsell, A.G]]
		+	[[Category: Schuler, H]]
		+	[[Category: Karlberg, T]]

OCA at 08:23, 10 September 2014

OCA — Wed, 10 Sep 2014 08:23:00 GMT

←Older revision		Revision as of 08:23, 10 September 2014
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4r5w is ON HOLD	+	The entry 4r5w is ON HOLD until Paper Publication

	Authors: Karlberg, T., Thorsell, A.G., Schuler, H.		Authors: Karlberg, T., Thorsell, A.G., Schuler, H.

	Description: Human artd1 (parp1) -catalytic domain in complex with inhibitor xav939		Description: Human artd1 (parp1) -catalytic domain in complex with inhibitor xav939

OCA: Protected "4r5w" [edit=sysop:move=sysop]

OCA — Thu, 04 Sep 2014 04:15:41 GMT

Protected "4r5w" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:15, 4 September 2014

OCA: New page: '''Unreleased structure''' The entry 4r5w is ON HOLD Authors: Karlberg, T., Thorsell, A.G., Schuler, H. Description: Human artd1 (parp1) -catalytic domain in complex with inhibitor xav...

OCA — Thu, 04 Sep 2014 04:15:40 GMT

New page: '''Unreleased structure''' The entry 4r5w is ON HOLD Authors: Karlberg, T., Thorsell, A.G., Schuler, H. Description: Human artd1 (parp1) -catalytic domain in complex with inhibitor xav...

New page

'''Unreleased structure'''

The entry 4r5w is ON HOLD

Authors: Karlberg, T., Thorsell, A.G., Schuler, H.

Description: Human artd1 (parp1) -catalytic domain in complex with inhibitor xav939