5gho - Revision history

OCA at 09:12, 20 March 2024

OCA — Wed, 20 Mar 2024 09:12:26 GMT

←Older revision		Revision as of 09:12, 20 March 2024
Line 10:		Line 10:
	== Function ==		== Function ==
	[https://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>		[https://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 ==
-	The human MutT homolog 1 (hMTH1, hNUDT1) hydrolyzes oxidatively damaged nucleoside triphosphates and is the main enzyme responsible for nucleotide sanitization. hMTH1 recently has received attention as an anti-cancer target because hMTH1 blockade leads to accumulation of oxidized nucleotides in the cell, resulting in mutations and death of cancer cells. Unlike Escherichia coli MutT, which shows high substrate specificity for 8-oxoguanine nucleotides, hMTH1 has broad substrate specificity for oxidized nucleotides, including 8-oxo-dGTP and 2-oxo-dATP. However, the reason for this broad substrate specificity remains unclear. Here, we determined crystal structures of hMTH1 in complex with 8-oxo-dGTP or 2-oxo-dATP at neutral pH. These structures based on high-quality data showed that the base moieties of two substrates are located on the similar but not the same position in the substrate-binding pocket and adopt a different hydrogen-bonding pattern and both triphosphate moieties bind to the hMTH1 Nudix motif (i.e. the hydrolase motif) similarly and align for the hydrolysis reaction. We also performed kinetic assays on the substrate-binding Asp120 mutants (D120N and D120A), and determined their crystal structures in complex with the substrates. Analyses of bond-lengths with high-resolution X-ray data and of the relation between the structure and enzymatic activity revealed that hMTH1 recognizes the different oxidized nucleotides via an exchange of the protonation state at two neighboring aspartate residues (Asp119 and Asp120) in its substrate-binding pocket. To our knowledge, this mechanism of broad substrate recognition by enzymes has not been reported previously and may have relevance for anti-cancer drug development strategies targeting hMTH1.
-
-	Structural and Kinetic Studies of the Human Nudix Hydrolase MTH1 Reveal the Mechanism for Its Broad Substrate Specificity.,Waz S, Nakamura T, Hirata K, Ogawa YK, Chirifu M, Arimori T, Tamada T, Ikemizu S, Nakabeppu Y, Yamagata Y J Biol Chem. 2016 Dec 29. pii: jbc.M116.749713. doi: 10.1074/jbc.M116.749713. PMID:28035004<ref>PMID:28035004</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 5gho" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 11:31, 2 August 2023

OCA — Wed, 02 Aug 2023 11:31:46 GMT

←Older revision		Revision as of 11:31, 2 August 2023
Line 3:		Line 3:
	<StructureSection load='5gho' size='340' side='right'caption='[[5gho]], [[Resolution\|resolution]] 1.19Å' scene=''>		<StructureSection load='5gho' size='340' side='right'caption='[[5gho]], [[Resolution\|resolution]] 1.19Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5gho]] is a 2 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=5GHO OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5GHO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5gho]] 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=5GHO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5GHO FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=8DG:8~~-~~OXO-2-DEOXYGUANOSINE-5-TRIPHOSPHATE'>8DG</scene>~~, ~~<scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 1.191Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat">~~[[5ghi\|5ghi]], [[5ghj\|5ghj]], [[5ghm\|5ghm]], [[5ghn\|5ghn]], [[5ghp\|5ghp]], [[5ghq\|5ghq]]~~<~~/td~~></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8DG:8-OXO-2-DEOXYGUANOSINE-5-TRIPHOSPHATE'>8DG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=5gho FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gho OCA], [https://pdbe.org/5gho PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5gho RCSB], [https://www.ebi.ac.uk/pdbsum/5gho PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5gho ProSAT]</span></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=5gho FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gho OCA], [~~http~~://pdbe.org/5gho PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5gho RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5gho PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5gho 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>	+	[https://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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Hirata, K]]	+	[[Category: Hirata K]]
-	[[Category: Nakabeppu, Y]]	+	[[Category: Nakabeppu Y]]
-	[[Category: Nakamura, T]]	+	[[Category: Nakamura T]]
-	[[Category: Waz, S]]	+	[[Category: Waz S]]
-	[[Category: Yamagata, Y]]	+	[[Category: Yamagata Y]]
-	~~[[Category: Alpha-beta-alpha sandwich]]~~	+
-	~~[[Category: Dna damage]]~~	+
-	~~[[Category: Dna repair]]~~	+
-	~~[[Category: Dna replication]]~~	+
-	~~[[Category: Hydrolase~~]]	+

OCA at 10:07, 26 February 2020

OCA — Wed, 26 Feb 2020 10:07:26 GMT

←Older revision		Revision as of 10:07, 26 February 2020
Line 1:		Line 1:

	==Crystal structure of human MTH1(G2K/D120A mutant) in complex with 8-oxo-dGTP==		==Crystal structure of human MTH1(G2K/D120A mutant) in complex with 8-oxo-dGTP==
-	<StructureSection load='5gho' size='340' side='right' caption='[[5gho]], [[Resolution\|resolution]] 1.19Å' scene=''>	+	<StructureSection load='5gho' size='340' side='right'caption='[[5gho]], [[Resolution\|resolution]] 1.19Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5gho]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GHO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5GHO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5gho]] is a 2 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=5GHO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5GHO FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8DG:8-OXO-2-DEOXYGUANOSINE-5-TRIPHOSPHATE'>8DG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8DG:8-OXO-2-DEOXYGUANOSINE-5-TRIPHOSPHATE'>8DG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5ghi\|5ghi]], [[5ghj\|5ghj]], [[5ghm\|5ghm]], [[5ghn\|5ghn]], [[5ghp\|5ghp]], [[5ghq\|5ghq]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5ghi\|5ghi]], [[5ghj\|5ghj]], [[5ghm\|5ghm]], [[5ghn\|5ghn]], [[5ghp\|5ghp]], [[5ghq\|5ghq]]</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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5gho FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gho OCA], [http://pdbe.org/5gho PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5gho RCSB], [http://www.ebi.ac.uk/pdbsum/5gho PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5gho ProSAT]</span></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=5gho FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gho OCA], [http://pdbe.org/5gho PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5gho RCSB], [http://www.ebi.ac.uk/pdbsum/5gho PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5gho ProSAT]</span></td></tr>
	</table>		</table>
Line 19:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 5gho" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5gho" 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: Hirata, K]]		[[Category: Hirata, K]]
	[[Category: Nakabeppu, Y]]		[[Category: Nakabeppu, Y]]

OCA at 07:36, 18 January 2017

OCA — Wed, 18 Jan 2017 07:36:24 GMT

←Older revision		Revision as of 07:36, 18 January 2017
Line 12:		Line 12:
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
-	~~Human MTH1~~ (hMTH1) ~~is an enzyme that hydrolyses several oxidized purine~~ nucleoside triphosphates ~~to their corresponding nucleoside monophosphates. Crystallographic studies have shown that~~ the ~~accurate mode of interaction between 8~~-~~oxoguanine and~~ hMTH1 ~~cannot be understood without determining the positions~~ of the ~~H atoms~~, ~~as can be observed~~ in ~~neutron~~ and~~/or ultrahigh-resolution X-ray diffraction studies~~. ~~The hMTH1 protein prepared in the original expression system from~~ Escherichia coli ~~did not appear to be suitable for obtaining~~ high-~~quality crystals because the~~ hMTH1 ~~protein had heterogeneous N~~-~~termini of Met1~~ and ~~Gly2 that resulted from N~~-~~terminal Met excision by methionine aminopeptidase from the E~~. ~~coli host. To obtain homogeneous hMTH1~~, the ~~Gly at the second position was replaced by Lys~~. ~~As a result~~, ~~mutant hMTH1 protein [~~hMTH1~~(G2K)]~~ with ~~a homogeneous N~~-~~terminus could be prepared and~~ high-quality ~~crystals which diffracted~~ to ~~near 1~~.~~1 A resolution using synchrotron radiation were produced~~. ~~The new crystals belonged to space group P2(1~~)2(~~1)2(1~~), with ~~unit~~-~~cell parameters a = 46~~.36, ~~b = 47.58, c = 123.89 A~~.	+	The human MutT homolog 1 (hMTH1, hNUDT1) hydrolyzes oxidatively damaged nucleoside triphosphates and is the main enzyme responsible for nucleotide sanitization. hMTH1 recently has received attention as an anti-cancer target because hMTH1 blockade leads to accumulation of oxidized nucleotides in the cell, resulting in mutations and death of cancer cells. Unlike Escherichia coli MutT, which shows high substrate specificity for 8-oxoguanine nucleotides, hMTH1 has broad substrate specificity for oxidized nucleotides, including 8-oxo-dGTP and 2-oxo-dATP. However, the reason for this broad substrate specificity remains unclear. Here, we determined crystal structures of hMTH1 in complex with 8-oxo-dGTP or 2-oxo-dATP at neutral pH. These structures based on high-quality data showed that the base moieties of two substrates are located on the similar but not the same position in the substrate-binding pocket and adopt a different hydrogen-bonding pattern and both triphosphate moieties bind to the hMTH1 Nudix motif (i.e. the hydrolase motif) similarly and align for the hydrolysis reaction. We also performed kinetic assays on the substrate-binding Asp120 mutants (D120N and D120A), and determined their crystal structures in complex with the substrates. Analyses of bond-lengths with high-resolution X-ray data and of the relation between the structure and enzymatic activity revealed that hMTH1 recognizes the different oxidized nucleotides via an exchange of the protonation state at two neighboring aspartate residues (Asp119 and Asp120) in its substrate-binding pocket. To our knowledge, this mechanism of broad substrate recognition by enzymes has not been reported previously and may have relevance for anti-cancer drug development strategies targeting hMTH1.

-	~~Crystallization~~ and ~~preliminary X-ray analysis~~ of ~~human~~ MTH1 ~~with a homogeneous N-terminus~~.,~~Koga Y, Inazato M~~, Nakamura T, ~~Hashikawa C~~, Chirifu M, ~~Michi A~~, ~~Yamashita~~ T~~, Toma S, Kuniyasu A~~, Ikemizu S, Nakabeppu Y, Yamagata Y ~~Acta Crystallogr Sect F Struct~~ Biol ~~Cryst Commun~~. ~~2013 Jan 1;69(Pt 1)~~:~~45-8~~. doi: , 10.~~1107~~/~~S1744309112048002~~. ~~Epub 2012 Dec 20~~. PMID:~~23295485~~<ref>PMID:~~23295485~~</ref>	+	Structural and Kinetic Studies of the Human Nudix Hydrolase MTH1 Reveal the Mechanism for Its Broad Substrate Specificity.,Waz S, Nakamura T, Hirata K, Ogawa YK, Chirifu M, Arimori T, Tamada T, Ikemizu S, Nakabeppu Y, Yamagata Y J Biol Chem. 2016 Dec 29. pii: jbc.M116.749713. doi: 10.1074/jbc.M116.749713. PMID:28035004<ref>PMID:28035004</ref>

	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

OCA at 16:39, 4 January 2017

OCA — Wed, 04 Jan 2017 16:39:01 GMT

←Older revision		Revision as of 16:39, 4 January 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5gho is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of human MTH1(G2K/D120A mutant) in complex with 8-oxo-dGTP==
		+	<StructureSection load='5gho' size='340' side='right' caption='[[5gho]], [[Resolution\|resolution]] 1.19Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5gho]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GHO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5GHO FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8DG:8-OXO-2-DEOXYGUANOSINE-5-TRIPHOSPHATE'>8DG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5ghi\|5ghi]], [[5ghj\|5ghj]], [[5ghm\|5ghm]], [[5ghn\|5ghn]], [[5ghp\|5ghp]], [[5ghq\|5ghq]]</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=5gho FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gho OCA], [http://pdbe.org/5gho PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5gho RCSB], [http://www.ebi.ac.uk/pdbsum/5gho PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5gho 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Human MTH1 (hMTH1) is an enzyme that hydrolyses several oxidized purine nucleoside triphosphates to their corresponding nucleoside monophosphates. Crystallographic studies have shown that the accurate mode of interaction between 8-oxoguanine and hMTH1 cannot be understood without determining the positions of the H atoms, as can be observed in neutron and/or ultrahigh-resolution X-ray diffraction studies. The hMTH1 protein prepared in the original expression system from Escherichia coli did not appear to be suitable for obtaining high-quality crystals because the hMTH1 protein had heterogeneous N-termini of Met1 and Gly2 that resulted from N-terminal Met excision by methionine aminopeptidase from the E. coli host. To obtain homogeneous hMTH1, the Gly at the second position was replaced by Lys. As a result, mutant hMTH1 protein [hMTH1(G2K)] with a homogeneous N-terminus could be prepared and high-quality crystals which diffracted to near 1.1 A resolution using synchrotron radiation were produced. The new crystals belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 46.36, b = 47.58, c = 123.89 A.

-	~~Authors~~:	+	Crystallization and preliminary X-ray analysis of human MTH1 with a homogeneous N-terminus.,Koga Y, Inazato M, Nakamura T, Hashikawa C, Chirifu M, Michi A, Yamashita T, Toma S, Kuniyasu A, Ikemizu S, Nakabeppu Y, Yamagata Y Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013 Jan 1;69(Pt 1):45-8. doi: , 10.1107/S1744309112048002. Epub 2012 Dec 20. PMID:23295485<ref>PMID:23295485</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5gho" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Hirata, K]]
		+	[[Category: Nakabeppu, Y]]
		+	[[Category: Nakamura, T]]
		+	[[Category: Waz, S]]
		+	[[Category: Yamagata, Y]]
		+	[[Category: Alpha-beta-alpha sandwich]]
		+	[[Category: Dna damage]]
		+	[[Category: Dna repair]]
		+	[[Category: Dna replication]]
		+	[[Category: Hydrolase]]

OCA: Protected "5gho" [edit=sysop:move=sysop]

OCA — Tue, 12 Jul 2016 21:34:13 GMT

Protected "5gho" [edit=sysop:move=sysop]

←Older revision

Revision as of 21:34, 12 July 2016

OCA: New page: '''Unreleased structure''' The entry 5gho is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

OCA — Tue, 12 Jul 2016 21:34:12 GMT

New page: '''Unreleased structure''' The entry 5gho is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5gho is ON HOLD until Paper Publication

Authors:

Description:
[[Category: Unreleased Structures]]