5xst - Revision history

OCA at 08:12, 22 November 2023

OCA — Wed, 22 Nov 2023 08:12:54 GMT

←Older revision		Revision as of 08:12, 22 November 2023
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	<StructureSection load='5xst' size='340' side='right'caption='[[5xst]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='5xst' size='340' side='right'caption='[[5xst]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5xst]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XST OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5XST FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5xst]] is a 1 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=5XST OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XST FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8E6:6-fluoranyl-2-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-1~{H}-benzimidazole-4-carboxamide'>8E6</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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='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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8E6:6-fluoranyl-2-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-1~{H}-benzimidazole-4-carboxamide'>8E6</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=5xst FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xst OCA], [~~http~~://pdbe.org/5xst PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5xst RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5xst PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5xst 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=5xst FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xst OCA], [https://pdbe.org/5xst PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xst RCSB], [https://www.ebi.ac.uk/pdbsum/5xst PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xst 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 ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Liu, Q]]	+	[[Category: Liu Q]]
-	[[Category: Xu, Y]]	+	[[Category: Xu Y]]
-	~~[[Category: Complex structure]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 06:58, 14 October 2020

OCA — Wed, 14 Oct 2020 06:58:22 GMT

←Older revision		Revision as of 06:58, 14 October 2020
Line 1:		Line 1:

	==novel orally efficacious inhibitors complexed with PARP1==		==novel orally efficacious inhibitors complexed with PARP1==
-	<StructureSection load='5xst' size='340' side='right' caption='[[5xst]], [[Resolution\|resolution]] 2.30Å' scene=''>	+	<StructureSection load='5xst' size='340' side='right'caption='[[5xst]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5xst]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XST OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5XST FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5xst]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XST OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5XST FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8E6:6-fluoranyl-2-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-1~{H}-benzimidazole-4-carboxamide'>8E6</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8E6:6-fluoranyl-2-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-1~{H}-benzimidazole-4-carboxamide'>8E6</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=5xst FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xst OCA], [http://pdbe.org/5xst PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xst RCSB], [http://www.ebi.ac.uk/pdbsum/5xst PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xst 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=5xst FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xst OCA], [http://pdbe.org/5xst PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xst RCSB], [http://www.ebi.ac.uk/pdbsum/5xst PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xst ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5xst" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5xst" 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: Large Structures]]
	[[Category: Liu, Q]]		[[Category: Liu, Q]]
	[[Category: Xu, Y]]		[[Category: Xu, Y]]
	[[Category: Complex structure]]		[[Category: Complex structure]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 05:29, 25 April 2018

OCA — Wed, 25 Apr 2018 05:29:23 GMT

←Older revision		Revision as of 05:29, 25 April 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5xst is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==novel orally efficacious inhibitors complexed with PARP1==
		+	<StructureSection load='5xst' size='340' side='right' caption='[[5xst]], [[Resolution\|resolution]] 2.30Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5xst]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XST OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XST FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8E6:6-fluoranyl-2-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)-1~{H}-benzimidazole-4-carboxamide'>8E6</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=5xst FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xst OCA], [http://pdbe.org/5xst PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xst RCSB], [http://www.ebi.ac.uk/pdbsum/5xst PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xst ProSAT]</span></td></tr>
		+	</table>
		+	== 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The nuclear protein poly(ADP-ribose) polymerases-1/2 (PARP-1/2) are involved in DNA repair damaged by endogenous or exogenous process. And PARP-1/2 inhibitors have been proved to be clinically efficacious for DNA repair deficient tumors in the past decade. We have developed a series of 4,5,6,7-tetrahydrothienopyridin-2-yl benzimidazole carboxamides as novel and potent PARP-1/2 inhibitors. The best compound resulted from this series is compound 27 which displays excellent PARP-1 and PARP-2 inhibitory activity with IC50 of 18nM and 42nM, respectively. Furthermore, it can selectively kill BRCA2 deficient V-C8 cells with a CC50 of 920nM. In the MDA-MB-436 (BRCA-1 mutant) xenograft model, this compound was well tolerated and showed single-agent activity. Based on the results above, compound 27 has been selected as a lead candidate targeting PARP-1/2 and its preclinical characterization is also underway.

-	~~Authors:~~ Liu, Q~~.F.~~, Xu, Y.C.	+	Design and synthesis of 2-(4,5,6,7-tetrahydrothienopyridin-2-yl)-benzoimidazole carboxamides as novel orally efficacious Poly(ADP-ribose)polymerase (PARP) inhibitors.,Chen X, Huan X, Liu Q, Wang Y, He Q, Tan C, Chen Y, Ding J, Xu Y, Miao Z, Yang C Eur J Med Chem. 2018 Feb 10;145:389-403. doi: 10.1016/j.ejmech.2018.01.018. Epub , 2018 Jan 8. PMID:29335205<ref>PMID:29335205</ref>

-	~~Description~~: ~~novel orally efficacious inhibitors complexed with PARP1~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Xu, Y.C]]	+	<div class="pdbe-citations 5xst" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Liu, Q.F~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Liu, Q]]
		+	[[Category: Xu, Y]]
		+	[[Category: Complex structure]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA: Protected "5xst" [edit=sysop:move=sysop]

OCA — Wed, 27 Sep 2017 15:44:56 GMT

Protected "5xst" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:44, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5xst is ON HOLD until Paper Publication Authors: Liu, Q.F., Xu, Y.C. Description: novel orally efficacious inhibitors complexed with PARP1 [[Catego...

OCA — Wed, 27 Sep 2017 15:44:55 GMT

New page: '''Unreleased structure''' The entry 5xst is ON HOLD until Paper Publication Authors: Liu, Q.F., Xu, Y.C. Description: novel orally efficacious inhibitors complexed with PARP1 [[Catego...

New page

'''Unreleased structure'''

The entry 5xst is ON HOLD until Paper Publication

Authors: Liu, Q.F., Xu, Y.C.

Description: novel orally efficacious inhibitors complexed with PARP1
[[Category: Unreleased Structures]]
[[Category: Xu, Y.C]]
[[Category: Liu, Q.F]]