7z1y - Revision history

OCA at 08:01, 7 February 2024

OCA — Wed, 07 Feb 2024 08:01:28 GMT

←Older revision		Revision as of 08:01, 7 February 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7z1y]] 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=7Z1Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Z1Y FirstGlance]. <br>		<table><tr><td colspan='2'>[[7z1y]] 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=7Z1Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Z1Y FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=I5F:[1,2,4]triazolo[3,4-b][1,3]benzothiazol-6-ol'>I5F</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]] 1.75Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=I5F:[1,2,4]triazolo[3,4-b][1,3]benzothiazol-6-ol'>I5F</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=7z1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7z1y OCA], [https://pdbe.org/7z1y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7z1y RCSB], [https://www.ebi.ac.uk/pdbsum/7z1y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7z1y 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=7z1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7z1y OCA], [https://pdbe.org/7z1y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7z1y RCSB], [https://www.ebi.ac.uk/pdbsum/7z1y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7z1y ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/PAR15_HUMAN PAR15_HUMAN] Transcriptional repressor. Has ADP-ribosyltransferase activity.		[https://www.uniprot.org/uniprot/PAR15_HUMAN PAR15_HUMAN] Transcriptional repressor. Has ADP-ribosyltransferase activity.
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	We report [1,2,4]triazolo[3,4-b]benzothiazole (TBT) as a new inhibitor scaffold, which competes with nicotinamide in the binding pocket of human poly- and mono-ADP-ribosylating enzymes. The binding mode was studied through analogues and cocrystal structures with TNKS2, PARP2, PARP14, and PARP15. Based on the substitution pattern, we were able to identify 3-amino derivatives 21 (OUL243) and 27 (OUL232) as inhibitors of mono-ARTs PARP7, PARP10, PARP11, PARP12, PARP14, and PARP15 at nM potencies, with 27 being the most potent PARP10 inhibitor described to date (IC(50) of 7.8 nM) and the first PARP12 inhibitor ever reported. On the contrary, hydroxy derivative 16 (OUL245) inhibits poly-ARTs with a selectivity toward PARP2. The scaffold does not possess inherent cell toxicity, and the inhibitors can enter cells and engage with the target protein. This, together with favorable ADME properties, demonstrates the potential of TBT scaffold for future drug development efforts toward selective inhibitors against specific enzymes.

-	[1,2,4]Triazolo[3,4-b]benzothiazole Scaffold as Versatile Nicotinamide Mimic Allowing Nanomolar Inhibition of Different PARP Enzymes.,Murthy S, Nizi MG, Maksimainen MM, Massari S, Alaviuhkola J, Lippok BE, Vagaggini C, Sowa ST, Galera-Prat A, Ashok Y, Venkannagari H, Prunskaite-Hyyrylainen R, Dreassi E, Luscher B, Korn P, Tabarrini O, Lehtio L J Med Chem. 2023 Jan 4. doi: 10.1021/acs.jmedchem.2c01460. PMID:36598465<ref>PMID:36598465</ref>	+	==See Also==
-		+	*[[Poly(ADP-ribose) polymerase 3D structures\|Poly(ADP-ribose) polymerase 3D structures]]
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class~~=~~"pdbe-citations 7z1y" style~~=~~"background-color:#fffaf0;"></div>~~	+
-	~~== References~~ ==	+
-	~~<references/>~~	+
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 06:33, 25 January 2023

OCA — Wed, 25 Jan 2023 06:33:53 GMT

←Older revision		Revision as of 06:33, 25 January 2023
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7z1y is ~~ON HOLD until Paper~~ Publication	+	==PARP15 catalytic domain in complex with OUL245==
		+	<StructureSection load='7z1y' size='340' side='right'caption='[[7z1y]], [[Resolution\|resolution]] 1.75Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7z1y]] 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=7Z1Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Z1Y FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=I5F:[1,2,4]triazolo[3,4-b][1,3]benzothiazol-6-ol'>I5F</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=7z1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7z1y OCA], [https://pdbe.org/7z1y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7z1y RCSB], [https://www.ebi.ac.uk/pdbsum/7z1y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7z1y ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/PAR15_HUMAN PAR15_HUMAN] Transcriptional repressor. Has ADP-ribosyltransferase activity.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	We report [1,2,4]triazolo[3,4-b]benzothiazole (TBT) as a new inhibitor scaffold, which competes with nicotinamide in the binding pocket of human poly- and mono-ADP-ribosylating enzymes. The binding mode was studied through analogues and cocrystal structures with TNKS2, PARP2, PARP14, and PARP15. Based on the substitution pattern, we were able to identify 3-amino derivatives 21 (OUL243) and 27 (OUL232) as inhibitors of mono-ARTs PARP7, PARP10, PARP11, PARP12, PARP14, and PARP15 at nM potencies, with 27 being the most potent PARP10 inhibitor described to date (IC(50) of 7.8 nM) and the first PARP12 inhibitor ever reported. On the contrary, hydroxy derivative 16 (OUL245) inhibits poly-ARTs with a selectivity toward PARP2. The scaffold does not possess inherent cell toxicity, and the inhibitors can enter cells and engage with the target protein. This, together with favorable ADME properties, demonstrates the potential of TBT scaffold for future drug development efforts toward selective inhibitors against specific enzymes.

-	~~Authors~~:	+	[1,2,4]Triazolo[3,4-b]benzothiazole Scaffold as Versatile Nicotinamide Mimic Allowing Nanomolar Inhibition of Different PARP Enzymes.,Murthy S, Nizi MG, Maksimainen MM, Massari S, Alaviuhkola J, Lippok BE, Vagaggini C, Sowa ST, Galera-Prat A, Ashok Y, Venkannagari H, Prunskaite-Hyyrylainen R, Dreassi E, Luscher B, Korn P, Tabarrini O, Lehtio L J Med Chem. 2023 Jan 4. doi: 10.1021/acs.jmedchem.2c01460. PMID:36598465<ref>PMID:36598465</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 7z1y" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Lehtio L]]
		+	[[Category: Maksimainen MM]]

OCA at 09:18, 6 April 2022

OCA — Wed, 06 Apr 2022 09:18:55 GMT

←Older revision		Revision as of 09:18, 6 April 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7z1y is ON HOLD	+	The entry 7z1y is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7z1y" [edit=sysop:move=sysop]

OCA — Wed, 09 Mar 2022 05:09:45 GMT

Protected "7z1y" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:09, 9 March 2022

OCA: New page: '''Unreleased structure''' The entry 7z1y is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 09 Mar 2022 05:09:44 GMT

New page: '''Unreleased structure''' The entry 7z1y is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7z1y is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]