OCA at 07:25, 30 September 2020

OCA — Wed, 30 Sep 2020 07:25:39 GMT

←Older revision		Revision as of 07:25, 30 September 2020
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	<StructureSection load='6qvo' size='340' side='right'caption='[[6qvo]], [[Resolution\|resolution]] 2.45Å' scene=''>		<StructureSection load='6qvo' size='340' side='right'caption='[[6qvo]], [[Resolution\|resolution]] 2.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6qvo]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QVO OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6QVO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6qvo]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QVO OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6QVO FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6MA:N6-METHYL-DEOXY-ADENOSINE-5-MONOPHOSPHATE'>6MA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=6MA:N6-METHYL-DEOXY-ADENOSINE-5-MONOPHOSPHATE'>6MA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6qvo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qvo OCA], [http://pdbe.org/6qvo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qvo RCSB], [http://www.ebi.ac.uk/pdbsum/6qvo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qvo ProSAT]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NUDT1, MTH1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6qvo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qvo OCA], [http://pdbe.org/6qvo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qvo RCSB], [http://www.ebi.ac.uk/pdbsum/6qvo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qvo ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/8ODP_HUMAN 8ODP_HUMAN]] Antimutagenic. Acts as a sanitizing enzyme for oxidized nucleotide pools, thus suppressing cell dysfunction and death induced by oxidative stress. Hydrolyzes 8-oxo-dGTP, 8-oxo-dATP and 2-OH-dATP, thus preventing misincorporation of oxidized purine nucleoside triphosphates into DNA and subsequently preventing A:T to C:G and G:C to T:A transversions. Able to hydrolyze also the corresponding ribonucleotides, 2-OH-ATP, 8-oxo-GTP and 8-oxo-ATP.<ref>PMID:10373420</ref> <ref>PMID:10608900</ref> <ref>PMID:11139615</ref> <ref>PMID:12857738</ref> <ref>PMID:22556419</ref>		[[http://www.uniprot.org/uniprot/8ODP_HUMAN 8ODP_HUMAN]] Antimutagenic. Acts as a sanitizing enzyme for oxidized nucleotide pools, thus suppressing cell dysfunction and death induced by oxidative stress. Hydrolyzes 8-oxo-dGTP, 8-oxo-dATP and 2-OH-dATP, thus preventing misincorporation of oxidized purine nucleoside triphosphates into DNA and subsequently preventing A:T to C:G and G:C to T:A transversions. Able to hydrolyze also the corresponding ribonucleotides, 2-OH-ATP, 8-oxo-GTP and 8-oxo-ATP.<ref>PMID:10373420</ref> <ref>PMID:10608900</ref> <ref>PMID:11139615</ref> <ref>PMID:12857738</ref> <ref>PMID:22556419</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	MutT homologue 1 (MTH1) removes oxidized nucleotides from the nucleotide pool and thereby prevents their incorporation into the genome and thereby reduces genotoxicity. We previously reported that MTH1 is an efficient catalyst of O6-methyl-dGTP hydrolysis suggesting that MTH1 may also sanitize the nucleotide pool from other methylated nucleotides. We here show that MTH1 efficiently catalyzes the hydrolysis of N6-methyl-dATP to N6-methyl-dAMP and further report that N6-methylation of dATP drastically increases the MTH1 activity. We also observed MTH1 activity with N6-methyl-ATP, albeit at a lower level. We show that N6-methyl-dATP is incorporated into DNA in vivo, as indicated by increased N6-methyl-dA DNA levels in embryos developed from MTH1 knock-out zebrafish eggs microinjected with N6-methyl-dATP compared with noninjected embryos. N6-methyl-dATP activity is present in MTH1 homologues from distantly related vertebrates, suggesting evolutionary conservation and indicating that this activity is important. Of note, N6-methyl-dATP activity is unique to MTH1 among related NUDIX hydrolases. Moreover, we present the structure of N6-methyl-dAMP-bound human MTH1, revealing that the N6-methyl group is accommodated within a hydrophobic active-site subpocket explaining why N6-methyl-dATP is a good MTH1 substrate. N6-methylation of DNA and RNA has been reported to have epigenetic roles and to affect mRNA metabolism. We propose that MTH1 acts in concert with adenosine deaminase-like protein isoform 1 (ADAL1) to prevent incorporation of N6-methyl-(d)ATP into DNA and RNA. This would hinder potential dysregulation of epigenetic control and RNA metabolism via conversion of N6-methyl-(d)ATP to N6-methyl-(d)AMP, followed by ADAL1-catalyzed deamination producing (d)IMP that can enter the nucleotide salvage pathway.
		+
		+	MutT homologue 1 (MTH1) removes N6-methyl-dATP from the dNTP pool.,Scaletti ER, Vallin KS, Brautigam L, Sarno A, Warpman Berglund U, Helleday T, Stenmark P, Jemth AS J Biol Chem. 2020 Apr 10;295(15):4761-4772. doi: 10.1074/jbc.RA120.012636. Epub, 2020 Mar 6. PMID:32144205<ref>PMID:32144205</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6qvo" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[7%2C8-dihydro-8-oxoguanine triphosphatase 3D structures\|7%2C8-dihydro-8-oxoguanine triphosphatase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Berglund, U Warpman]]		[[Category: Berglund, U Warpman]]

OCA at 09:48, 18 March 2020

OCA — Wed, 18 Mar 2020 09:48:48 GMT

←Older revision		Revision as of 09:48, 18 March 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6qvo is ~~ON HOLD~~	+	==Crystal structure of human MTH1 in complex with N6-methyl-dAMP==
-		+	<StructureSection load='6qvo' size='340' side='right'caption='[[6qvo]], [[Resolution\|resolution]] 2.45Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6qvo]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QVO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QVO FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6MA:N6-METHYL-DEOXY-ADENOSINE-5-MONOPHOSPHATE'>6MA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<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=6qvo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qvo OCA], [http://pdbe.org/6qvo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qvo RCSB], [http://www.ebi.ac.uk/pdbsum/6qvo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qvo ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/8ODP_HUMAN 8ODP_HUMAN]] Antimutagenic. Acts as a sanitizing enzyme for oxidized nucleotide pools, thus suppressing cell dysfunction and death induced by oxidative stress. Hydrolyzes 8-oxo-dGTP, 8-oxo-dATP and 2-OH-dATP, thus preventing misincorporation of oxidized purine nucleoside triphosphates into DNA and subsequently preventing A:T to C:G and G:C to T:A transversions. Able to hydrolyze also the corresponding ribonucleotides, 2-OH-ATP, 8-oxo-GTP and 8-oxo-ATP.<ref>PMID:10373420</ref> <ref>PMID:10608900</ref> <ref>PMID:11139615</ref> <ref>PMID:12857738</ref> <ref>PMID:22556419</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Berglund, U Warpman]]
		+	[[Category: Brautigam, L]]
		+	[[Category: Helleday, T]]
		+	[[Category: Jemth, A S]]
		+	[[Category: Sarno, A]]
		+	[[Category: Scaletti, E]]
		+	[[Category: Stenmark, P]]
		+	[[Category: Vallin, K S]]
		+	[[Category: Hydrolase]]

OCA: Protected "6qvo" [edit=sysop:move=sysop]

OCA — Wed, 13 Mar 2019 10:24:48 GMT

Protected "6qvo" [edit=sysop:move=sysop]

←Older revision

Revision as of 10:24, 13 March 2019

OCA: New page: '''Unreleased structure''' The entry 6qvo is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 13 Mar 2019 10:24:46 GMT

New page: '''Unreleased structure''' The entry 6qvo is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6qvo is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

6qvo - Revision history

OCA at 07:25, 30 September 2020

OCA at 09:48, 18 March 2020

OCA: Protected "6qvo" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 6qvo is ON HOLD Authors: Description: Category: Unreleased Structures