7pwa - Revision history

OCA at 13:10, 1 February 2024

OCA — Thu, 01 Feb 2024 13:10:03 GMT

←Older revision		Revision as of 13:10, 1 February 2024
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	==PARP15 catalytic domain in complex with OUL237==		==PARP15 catalytic domain in complex with OUL237==
-	<StructureSection load='7pwa' size='340' side='right'caption='[[7pwa]]' scene=''>	+	<StructureSection load='7pwa' size='340' side='right'caption='[[7pwa]], [[Resolution\|resolution]] 1.60Å' 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=7PWA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PWA FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7pwa]] 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=7PWA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PWA 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=7pwa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pwa OCA], [https://pdbe.org/7pwa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pwa RCSB], [https://www.ebi.ac.uk/pdbsum/7pwa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pwa 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]] 1.6Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8CI:4-(cyclopentylmethoxy)benzamide'>8CI</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</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=7pwa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pwa OCA], [https://pdbe.org/7pwa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pwa RCSB], [https://www.ebi.ac.uk/pdbsum/7pwa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pwa ProSAT]</span></td></tr>
	</table>		</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 ==
		+	While human poly-ADP-ribose chain generating poly-ARTs, PARP1 and 2 and TNKS1 and 2, have been widely characterized, less is known on the pathophysiological roles of the mono-ADP-ribosylating mono-ARTs, partly due to the lack of selective inhibitors. In this context, we have focused on the development of inhibitors for the mono-ART PARP10, whose overexpression is known to induce cell death. Starting from OUL35 (1) and its 4-(benzyloxy)benzamidic derivative (2) we herein report the design and synthesis of new analogues from which the cyclobutyl derivative 3c rescued cells most efficiently from PARP10 induced apoptosis. Most importantly, we also identified 2,3-dihydrophthalazine-1,4-dione as a new suitable nicotinamide mimicking PARP10 inhibitor scaffold. When it was functionalized with cycloalkyl (8a-c), o-fluorophenyl (8h), and thiophene (8l) rings, IC50 values in the 130-160 nM range were obtained, making them the most potent PARP10 inhibitors reported to date. These compounds also inhibited PARP15 with low micromolar IC50s, but none of the other tested poly- and mono-ARTs, thus emerging as dual mono-ART inhibitors. Compounds 8a, 8h and 8l were also able to enter cells and rescue cells from apoptosis. Our work sheds more light on inhibitor development against mono-ARTs and identifies chemical probes to study the cellular roles of PARP10 and PARP15.
		+
		+	Potent 2,3-dihydrophthalazine-1,4-dione derivatives as dual inhibitors for mono-ADP-ribosyltransferases PARP10 and PARP15.,Nizi MG, Maksimainen MM, Murthy S, Massari S, Alaviuhkola J, Lippok BE, Sowa ST, Galera-Prat A, Prunskaite-Hyyrylainen R, Luscher B, Korn P, Lehtio L, Tabarrini O Eur J Med Chem. 2022 Apr 19;237:114362. doi: 10.1016/j.ejmech.2022.114362. PMID:35500474<ref>PMID:35500474</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7pwa" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[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: Lehtio L]]		[[Category: Lehtio L]]
	[[Category: Maksimainen MM]]		[[Category: Maksimainen MM]]

OCA at 06:19, 12 May 2022

OCA — Thu, 12 May 2022 06:19:14 GMT

←Older revision		Revision as of 06:19, 12 May 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7pwa ~~is ON HOLD until Paper Publication~~	+	==PARP15 catalytic domain in complex with OUL237==
-		+	<StructureSection load='7pwa' size='340' side='right'caption='[[7pwa]]' scene=''>
-	~~Authors~~: ~~Maksimainen~~, M.M., ~~Lehtio~~, L.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PWA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PWA FirstGlance]. <br>
-	~~Description: PARP15 catalytic domain in complex with OUL237~~	+	</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=7pwa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7pwa OCA], [https://pdbe.org/7pwa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7pwa RCSB], [https://www.ebi.ac.uk/pdbsum/7pwa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7pwa ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Maksimainen, M.M~~]]	+	__TOC__
-	[[Category: ~~Lehtio, L~~]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Lehtio L]]
		+	[[Category: Maksimainen MM]]

OCA at 05:07, 10 November 2021

OCA — Wed, 10 Nov 2021 05:07:37 GMT

←Older revision		Revision as of 05:07, 10 November 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Maksimainen, M.M., Lehtio, L.		Authors: Maksimainen, M.M., Lehtio, L.

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

OCA — Wed, 13 Oct 2021 10:16:55 GMT

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

←Older revision

Revision as of 10:16, 13 October 2021

OCA: New page: '''Unreleased structure''' The entry 7pwa is ON HOLD Authors: Maksimainen, M.M., Lehtio, L. Description: PARP15 catalytic domain in complex with OUL237 [[Category: Unreleased Structure...

OCA — Wed, 13 Oct 2021 10:16:54 GMT

New page: '''Unreleased structure''' The entry 7pwa is ON HOLD Authors: Maksimainen, M.M., Lehtio, L. Description: PARP15 catalytic domain in complex with OUL237 [[Category: Unreleased Structure...

New page

'''Unreleased structure'''

The entry 7pwa is ON HOLD

Authors: Maksimainen, M.M., Lehtio, L.

Description: PARP15 catalytic domain in complex with OUL237
[[Category: Unreleased Structures]]
[[Category: Maksimainen, M.M]]
[[Category: Lehtio, L]]