7ufy - Revision history

OCA at 09:52, 25 October 2023

OCA — Wed, 25 Oct 2023 09:52:39 GMT

←Older revision		Revision as of 09:52, 25 October 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7ufy]] 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=7UFY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UFY FirstGlance]. <br>		<table><tr><td colspan='2'>[[7ufy]] 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=7UFY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UFY FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=N8I:[(4-{[(4S)-2,7-diphenylimidazo[1,2-a]pyridin-3-yl]amino}phenyl)methyl]phosphonic+acid'>N8I</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]] 1.584Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=N8I:[(4-{[(4S)-2,7-diphenylimidazo[1,2-a]pyridin-3-yl]amino}phenyl)methyl]phosphonic+acid'>N8I</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=7ufy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ufy OCA], [https://pdbe.org/7ufy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ufy RCSB], [https://www.ebi.ac.uk/pdbsum/7ufy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ufy 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=7ufy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ufy OCA], [https://pdbe.org/7ufy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ufy RCSB], [https://www.ebi.ac.uk/pdbsum/7ufy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ufy ProSAT]</span></td></tr>
	</table>		</table>
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	</div>		</div>
	<div class="pdbe-citations 7ufy" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7ufy" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Phosphodiesterase 3D structures\|Phosphodiesterase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 20:26, 12 April 2023

OCA — Wed, 12 Apr 2023 20:26:33 GMT

←Older revision		Revision as of 20:26, 12 April 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 7ufy is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of TDP1 complexed with compound XZ766==
		+	<StructureSection load='7ufy' size='340' side='right'caption='[[7ufy]], [[Resolution\|resolution]] 1.58Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7ufy]] 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=7UFY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UFY FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=N8I:[(4-{[(4S)-2,7-diphenylimidazo[1,2-a]pyridin-3-yl]amino}phenyl)methyl]phosphonic+acid'>N8I</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=7ufy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ufy OCA], [https://pdbe.org/7ufy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ufy RCSB], [https://www.ebi.ac.uk/pdbsum/7ufy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ufy ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/TYDP1_HUMAN TYDP1_HUMAN] Defects in TDP1 are the cause of spinocerebellar ataxia autosomal recessive with axonal neuropathy (SCAN1) [MIM:[https://omim.org/entry/607250 607250]. SCAN1 is an autosomal recessive cerebellar ataxia (ARCA) associated with peripheral axonal motor and sensory neuropathy, distal muscular atrophy, pes cavus and steppage gait as seen in Charcot-Marie-Tooth neuropathy. All affected individuals have normal intelligence.<ref>PMID:16141202</ref> <ref>PMID:15647511</ref> <ref>PMID:12244316</ref> <ref>PMID:17948061</ref> <ref>PMID:15920477</ref>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/TYDP1_HUMAN TYDP1_HUMAN] DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 3'-phosphodiester bond, giving rise to DNA with a free 3' phosphate. Catalyzes the hydrolysis of dead-end complexes between DNA and the topoisomerase I active site tyrosine residue. Hydrolyzes 3'-phosphoglycolates on protruding 3' ends on DNA double-strand breaks due to DNA damage by radiation and free radicals. Acts on blunt-ended double-strand DNA breaks and on single-stranded DNA. Has low 3'exonuclease activity and can remove a single nucleoside from the 3'end of DNA and RNA molecules with 3'hydroxyl groups. Has no exonuclease activity towards DNA or RNA with a 3'phosphate.<ref>PMID:12023295</ref> <ref>PMID:15111055</ref> <ref>PMID:15811850</ref> <ref>PMID:16141202</ref> <ref>PMID:22822062</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Tyrosyl-DNA phosphodiesterase 1 (TDP1) repairs stalled type I topoisomerase (TOP1)-DNA complexes by hydrolyzing the phosphodiester bond between the TOP1 Y723 residue and the 3'-phosphate of its DNA substrate. Although TDP1 antagonists could potentially reduce the dose of TOP1 inhibitors needed to achieve effective anticancer effects, the development of validated TDP1 inhibitors has proven to be challenging. This may, in part, be due to the open and extended nature of the TOP1 substrate binding region. We have previously reported imidazopyrazines and imidazopyridines that can inhibit TDP1 catalytic function in vitro. We solved the TDP1 crystal structures with bound inhibitors of this class and found that the dicarboxylic acid functionality within the N-(3,4-dicarboxyphenyl)-2-diphenylimidazo [1,2-a]pyridin-3-amine platform overlaps with aspects of phosphoryl substrate recognition. Yet phosphonic acids could potentially better-replicate cognate TOP1-DNA substrate binding interactions than carboxylic acids. As reported herein, we designed phosphonic acid-containing variants of our previously reported carboxylic acid-containing imidazopyrazine and imidazopyridine inhibitors and effected their synthesis using one-pot Groebke-Blackburn-Bienayme multicomponent reactions. We obtained crystal structures of TDP1 complexed with a subset of inhibitors. We discuss binding interactions of these inhibitors within the context of phosphate-containing substrate and carboxylic acid-based inhibitors. These compounds represent a new structural class of small molecule ligands that mimic aspects of the 3'-processed substrate that results from TDP1 catalysis.

-	~~Authors: Lountos, G.T~~., Zhao~~, X.Z.~~, Wang, W., Tropea~~, J.E.~~, Needle, D., Pommier, Y., Burke, ~~T.R~~.	+	Phosphonic acid-containing inhibitors of tyrosyl-DNA phosphodiesterase 1.,Zhao XZ, Wang W, Lountos GT, Tropea JE, Needle D, Pommier Y, Burke TR Jr Front Chem. 2022 Aug 16;10:910953. doi: 10.3389/fchem.2022.910953. eCollection , 2022. PMID:36051621<ref>PMID:36051621</ref>

-	~~Description: Crystal structure~~ of ~~TDP1 complexed with compound XZ766~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Wang, W~~]]	+	<div class="pdbe-citations 7ufy" style="background-color:#fffaf0;"></div>
-	[[Category: Lountos~~, G.T~~]]	+	== References ==
-	[[Category: ~~Burke, T.R~~]]	+	<references/>
-	[[Category: Pommier, Y]]	+	__TOC__
-	[[Category: ~~Zhao, X.Z~~]]	+	</StructureSection>
-	[[Category: ~~Tropea, J.E~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Needle, D~~]]	+	[[Category: Large Structures]]
		+	[[Category: Burke TR]]
		+	[[Category: Lountos GT]]
		+	[[Category: Needle D]]
		+	[[Category: Pommier Y]]
		+	[[Category: Tropea JE]]
		+	[[Category: Wang W]]
		+	[[Category: Zhao XZ]]

OCA at 06:43, 22 June 2022

OCA — Wed, 22 Jun 2022 06:43:54 GMT

←Older revision		Revision as of 06:43, 22 June 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Lountos, G.T., Zhao, X.Z., Wang, W., Tropea, J.E., Needle, D., Pommier, Y., Burke, T.R.		Authors: Lountos, G.T., Zhao, X.Z., Wang, W., Tropea, J.E., Needle, D., Pommier, Y., Burke, T.R.
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	Description: Crystal structure of TDP1 complexed with compound XZ766		Description: Crystal structure of TDP1 complexed with compound XZ766
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
		+	[[Category: Wang, W]]
		+	[[Category: Lountos, G.T]]
	[[Category: Burke, T.R]]		[[Category: Burke, T.R]]
	[[Category: Pommier, Y]]		[[Category: Pommier, Y]]
-	[[Category: Wang, W]]
	[[Category: Zhao, X.Z]]		[[Category: Zhao, X.Z]]
	[[Category: Tropea, J.E]]		[[Category: Tropea, J.E]]
	[[Category: Needle, D]]		[[Category: Needle, D]]
-	[[Category: Lountos, G.T]]

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

OCA — Wed, 30 Mar 2022 09:36:22 GMT

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

←Older revision

Revision as of 09:36, 30 March 2022

OCA: New page: '''Unreleased structure''' The entry 7ufy is ON HOLD Authors: Lountos, G.T., Zhao, X.Z., Wang, W., Tropea, J.E., Needle, D., Pommier, Y., Burke, T.R. Description: Crystal structure of ...

OCA — Wed, 30 Mar 2022 09:36:22 GMT

New page: '''Unreleased structure''' The entry 7ufy is ON HOLD Authors: Lountos, G.T., Zhao, X.Z., Wang, W., Tropea, J.E., Needle, D., Pommier, Y., Burke, T.R. Description: Crystal structure of ...

New page

'''Unreleased structure'''

The entry 7ufy is ON HOLD

Authors: Lountos, G.T., Zhao, X.Z., Wang, W., Tropea, J.E., Needle, D., Pommier, Y., Burke, T.R.

Description: Crystal structure of TDP1 complexed with compound XZ766
[[Category: Unreleased Structures]]
[[Category: Burke, T.R]]
[[Category: Pommier, Y]]
[[Category: Wang, W]]
[[Category: Zhao, X.Z]]
[[Category: Tropea, J.E]]
[[Category: Needle, D]]
[[Category: Lountos, G.T]]