7aop - Revision history

OCA at 12:13, 1 February 2024

OCA — Thu, 01 Feb 2024 12:13:11 GMT

←Older revision		Revision as of 12:13, 1 February 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7aop]] 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=7AOP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AOP FirstGlance]. <br>		<table><tr><td colspan='2'>[[7aop]] 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=7AOP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AOP FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=RTW:2-azanyl-9-cyclohexyl-8-(2-methoxyphenyl)-3~{H}-purine-6-thione'>RTW</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]] 2.35Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=RTW:2-azanyl-9-cyclohexyl-8-(2-methoxyphenyl)-3~{H}-purine-6-thione'>RTW</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=7aop FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aop OCA], [https://pdbe.org/7aop PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aop RCSB], [https://www.ebi.ac.uk/pdbsum/7aop PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aop 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=7aop FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aop OCA], [https://pdbe.org/7aop PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aop RCSB], [https://www.ebi.ac.uk/pdbsum/7aop PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aop ProSAT]</span></td></tr>
	</table>		</table>
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	</div>		</div>
	<div class="pdbe-citations 7aop" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7aop" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Nudix hydrolase 3D structures\|Nudix hydrolase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 10:05, 21 December 2022

OCA — Wed, 21 Dec 2022 10:05:37 GMT

←Older revision		Revision as of 10:05, 21 December 2022
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	<StructureSection load='7aop' size='340' side='right'caption='[[7aop]], [[Resolution\|resolution]] 2.35Å' scene=''>		<StructureSection load='7aop' size='340' side='right'caption='[[7aop]], [[Resolution\|resolution]] 2.35Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7aop]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AOP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AOP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7aop]] 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=7AOP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AOP FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=RTW:2-azanyl-9-cyclohexyl-8-(2-methoxyphenyl)-3~{H}-purine-6-thione'>RTW</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=RTW:2-azanyl-9-cyclohexyl-8-(2-methoxyphenyl)-3~{H}-purine-6-thione'>RTW</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7aom\|7aom]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NUDT15, MTH2 ([https://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/Nucleotide_diphosphatase Nucleotide diphosphatase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.9 3.6.1.9] </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=7aop FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aop OCA], [https://pdbe.org/7aop PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aop RCSB], [https://www.ebi.ac.uk/pdbsum/7aop PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aop 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=7aop FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aop OCA], [https://pdbe.org/7aop PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aop RCSB], [https://www.ebi.ac.uk/pdbsum/7aop PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aop ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/NUD15_HUMAN NUD15_HUMAN]] Mediates the hydrolysis of some nucleoside diphosphate derivatives. Can degrade 8-oxo-dGTP in vitro, suggesting that it may remove an oxidatively damaged form of guanine (7,8-dihydro-8-oxoguanine) from DNA and the nucleotide pool, thereby preventing misincorporation of 8-oxo-dGTP into DNA thus preventing A:T to C:G transversions. Its substrate specificity in vivo however remains unclear (By similarity). May have a role in DNA synthesis and cell cycle progression through the interaction with PCNA.<ref>PMID:19419956</ref> <ref>PMID:22556419</ref>	+	[https://www.uniprot.org/uniprot/NUD15_HUMAN NUD15_HUMAN] Mediates the hydrolysis of some nucleoside diphosphate derivatives. Can degrade 8-oxo-dGTP in vitro, suggesting that it may remove an oxidatively damaged form of guanine (7,8-dihydro-8-oxoguanine) from DNA and the nucleotide pool, thereby preventing misincorporation of 8-oxo-dGTP into DNA thus preventing A:T to C:G transversions. Its substrate specificity in vivo however remains unclear (By similarity). May have a role in DNA synthesis and cell cycle progression through the interaction with PCNA.<ref>PMID:19419956</ref> <ref>PMID:22556419</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 22:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Nucleotide diphosphatase]]~~	+	[[Category: Helleday T]]
-	[[Category: Helleday, T]]	+	[[Category: Rehling D]]
-	[[Category: Rehling, D]]	+	[[Category: Stenmark P]]
-	[[Category: Stenmark, P]]	+	[[Category: Zhang SM]]
-	[[Category: Zhang~~, S M]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Nudix hydrolase~~]]	+

OCA at 10:03, 14 July 2021

OCA — Wed, 14 Jul 2021 10:03:55 GMT

←Older revision		Revision as of 10:03, 14 July 2021
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	==Structure of NUDT15 in complex with inhibitor TH8321==		==Structure of NUDT15 in complex with inhibitor TH8321==
-	<StructureSection load='7aop' size='340' side='right'caption='[[7aop]]' scene=''>	+	<StructureSection load='7aop' size='340' side='right'caption='[[7aop]], [[Resolution\|resolution]] 2.35Å' 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=7AOP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AOP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7aop]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AOP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AOP 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=7aop FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aop OCA], [https://pdbe.org/7aop PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aop RCSB], [https://www.ebi.ac.uk/pdbsum/7aop PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aop ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=RTW:2-azanyl-9-cyclohexyl-8-(2-methoxyphenyl)-3~{H}-purine-6-thione'>RTW</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7aom\|7aom]]</div></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NUDT15, MTH2 ([https://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/Nucleotide_diphosphatase Nucleotide diphosphatase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.9 3.6.1.9] </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=7aop FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aop OCA], [https://pdbe.org/7aop PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aop RCSB], [https://www.ebi.ac.uk/pdbsum/7aop PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aop ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/NUD15_HUMAN NUD15_HUMAN]] Mediates the hydrolysis of some nucleoside diphosphate derivatives. Can degrade 8-oxo-dGTP in vitro, suggesting that it may remove an oxidatively damaged form of guanine (7,8-dihydro-8-oxoguanine) from DNA and the nucleotide pool, thereby preventing misincorporation of 8-oxo-dGTP into DNA thus preventing A:T to C:G transversions. Its substrate specificity in vivo however remains unclear (By similarity). May have a role in DNA synthesis and cell cycle progression through the interaction with PCNA.<ref>PMID:19419956</ref> <ref>PMID:22556419</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Ganciclovir (GCV) is the first-line therapy against human cytomegalovirus (HCMV), a widespread infection that is particularly dangerous for immunodeficient individuals. Closely resembling deoxyguanosine triphosphate, the tri-phosphorylated metabolite of GCV (GCV-TP) is preferentially incorporated by the viral DNA polymerase, thereby terminating chain extension and, eventually, viral replication. However, the treatment outcome of GCV varies greatly among individuals, therefore warranting better understanding of its metabolism. Here we show that NUDT15, a Nudix hydrolase known to metabolize thiopurine triphosphates, can similarly hydrolyze GCV-TP through biochemical studies and co-crystallization of the NUDT15/GCV-TP complex. More critically, GCV efficacy was potentiated in HCMV-infected cells following NUDT15 depletion by RNAi or inhibition by an in-house-developed, nanomolar NUDT15 inhibitor, TH8321, suggesting that pharmacological targeting of NUDT15 is a possible avenue to improve existing anti-HCMV regimens. Collectively, the data further implicate NUDT15 as a broad-spectrum metabolic regulator of nucleoside analog therapeutics, such as thiopurines and GCV.
		+
		+	NUDT15-mediated hydrolysis limits the efficacy of anti-HCMV drug ganciclovir.,Zhang SM, Rehling D, Jemth AS, Throup A, Landazuri N, Almlof I, Gottmann M, Valerie NCK, Borhade SR, Wakchaure P, Page BDG, Desroses M, Homan EJ, Scobie M, Rudd SG, Berglund UW, Soderberg-Naucler C, Stenmark P, Helleday T Cell Chem Biol. 2021 Jun 22. pii: S2451-9456(21)00268-3. doi:, 10.1016/j.chembiol.2021.06.001. PMID:34192523<ref>PMID:34192523</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7aop" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Helleday T]]	+	[[Category: Nucleotide diphosphatase]]
-	[[Category: Rehling D]]	+	[[Category: Helleday, T]]
-	[[Category: Stenmark P]]	+	[[Category: Rehling, D]]
-	[[Category: Zhang SM]]	+	[[Category: Stenmark, P]]
		+	[[Category: Zhang, S M]]
		+	[[Category: Hydrolase]]
		+	[[Category: Inhibitor]]
		+	[[Category: Nudix hydrolase]]

OCA at 14:34, 2 June 2021

OCA — Wed, 02 Jun 2021 14:34:07 GMT

←Older revision		Revision as of 14:34, 2 June 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7aop is ~~ON HOLD until Paper Publication~~	+	==Structure of NUDT15 in complex with inhibitor TH8321==
-		+	<StructureSection load='7aop' size='340' side='right'caption='[[7aop]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AOP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AOP FirstGlance]. <br>
-	~~Description~~:	+	</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=7aop FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aop OCA], [https://pdbe.org/7aop PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aop RCSB], [https://www.ebi.ac.uk/pdbsum/7aop PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aop ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Helleday T]]
		+	[[Category: Rehling D]]
		+	[[Category: Stenmark P]]
		+	[[Category: Zhang SM]]

OCA at 07:50, 18 November 2020

OCA — Wed, 18 Nov 2020 07:50:05 GMT

←Older revision		Revision as of 07:50, 18 November 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

OCA — Wed, 21 Oct 2020 06:39:54 GMT

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

←Older revision

Revision as of 06:39, 21 October 2020

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

OCA — Wed, 21 Oct 2020 06:39:53 GMT

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

New page

'''Unreleased structure'''

The entry 7aop is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]