8i1a - Revision history

OCA at 19:52, 29 May 2024

OCA — Wed, 29 May 2024 19:52:22 GMT

←Older revision		Revision as of 19:52, 29 May 2024
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	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
-	Human MutT homolog 1 (MTH1), also known as Nudix type motif 1 (NUDT1), hydrolyzes 8-oxo-dGTP and 2-oxo-dATP with broad substrate recognition and has attracted attention in ~~anti-cancer~~ therapeutics. Previous studies on MTH1 have proposed that the exchange of the protonation state between Asp119 and Asp120 is essential for the broad substrate recognition of MTH1. To understand the relationship between protonation states and substrate binding, we determined the crystal structures of MTH1 at pH 7.7-9.7. With increasing pH, MTH1 gradually loses its substrate-binding ability, indicating that Asp119 is deprotonated at pH 8.0-9.1 in 8-oxo-dGTP recognition and Asp120 is deprotonated at pH 8.6-9.7 in 2-oxo-dATP recognition. These results confirm that MTH1 recognizes 8-oxo-dGTP and 2-oxo-dATP by exchanging the protonation state between Asp119 and Asp120 with higher pK(a) .	+	Human MutT homolog 1 (MTH1), also known as Nudix-type motif 1 (NUDT1), hydrolyzes 8-oxo-dGTP and 2-oxo-dATP with broad substrate recognition and has attracted attention in anticancer therapeutics. Previous studies on MTH1 have proposed that the exchange of the protonation state between Asp119 and Asp120 is essential for the broad substrate recognition of MTH1. To understand the relationship between protonation states and substrate binding, we determined the crystal structures of MTH1 at pH 7.7-9.7. With increasing pH, MTH1 gradually loses its substrate-binding ability, indicating that Asp119 is deprotonated at pH 8.0-9.1 in 8-oxo-dGTP recognition and Asp120 is deprotonated at pH 8.6-9.7 in 2-oxo-dATP recognition. These results confirm that MTH1 recognizes 8-oxo-dGTP and 2-oxo-dATP by exchanging the protonation state between Asp119 and Asp120 with higher pK(a) .

-	Protonation states of Asp residues in the human Nudix hydrolase MTH1 contribute to its broad substrate recognition.,Nakamura T, Koga-Ogawa Y, Fujimiya K, Chirifu M, Goto M, Ikemizu S, Nakabeppu Y, Yamagata Y FEBS Lett. 2023 ~~Mar~~ 13. doi: 10.1002/1873-3468.14611. PMID:36914375<ref>PMID:36914375</ref>	+	Protonation states of Asp residues in the human Nudix hydrolase MTH1 contribute to its broad substrate recognition.,Nakamura T, Koga-Ogawa Y, Fujimiya K, Chirifu M, Goto M, Ikemizu S, Nakabeppu Y, Yamagata Y FEBS Lett. 2023 Jul;597(13):1770-1778. doi: 10.1002/1873-3468.14611. Epub 2023 , Mar 23. PMID:36914375<ref>PMID:36914375</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 12:56, 26 July 2023

OCA — Wed, 26 Jul 2023 12:56:11 GMT

←Older revision		Revision as of 12:56, 26 July 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[8i1a]] 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=8I1A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8I1A FirstGlance]. <br>		<table><tr><td colspan='2'>[[8i1a]] 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=8I1A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8I1A FirstGlance]. <br>
-	</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=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]] 1.4Å</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=NA:SODIUM+ION'>NA</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=8i1a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8i1a OCA], [https://pdbe.org/8i1a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8i1a RCSB], [https://www.ebi.ac.uk/pdbsum/8i1a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8i1a 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=8i1a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8i1a OCA], [https://pdbe.org/8i1a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8i1a RCSB], [https://www.ebi.ac.uk/pdbsum/8i1a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8i1a ProSAT]</span></td></tr>
	</table>		</table>

OCA at 07:29, 22 March 2023

OCA — Wed, 22 Mar 2023 07:29:07 GMT

←Older revision		Revision as of 07:29, 22 March 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 8i1a is ~~ON HOLD until Paper~~ Publication	+	==Crystal structure of human MTH1(G2K mutant) in complex with 8-oxo-dGTP at pH 8.6==
		+	<StructureSection load='8i1a' size='340' side='right'caption='[[8i1a]], [[Resolution\|resolution]] 1.40Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8i1a]] 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=8I1A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8I1A FirstGlance]. <br>
		+	</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=NA:SODIUM+ION'>NA</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=8i1a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8i1a OCA], [https://pdbe.org/8i1a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8i1a RCSB], [https://www.ebi.ac.uk/pdbsum/8i1a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8i1a ProSAT]</span></td></tr>
		+	</table>
		+	== 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Human MutT homolog 1 (MTH1), also known as Nudix type motif 1 (NUDT1), hydrolyzes 8-oxo-dGTP and 2-oxo-dATP with broad substrate recognition and has attracted attention in anti-cancer therapeutics. Previous studies on MTH1 have proposed that the exchange of the protonation state between Asp119 and Asp120 is essential for the broad substrate recognition of MTH1. To understand the relationship between protonation states and substrate binding, we determined the crystal structures of MTH1 at pH 7.7-9.7. With increasing pH, MTH1 gradually loses its substrate-binding ability, indicating that Asp119 is deprotonated at pH 8.0-9.1 in 8-oxo-dGTP recognition and Asp120 is deprotonated at pH 8.6-9.7 in 2-oxo-dATP recognition. These results confirm that MTH1 recognizes 8-oxo-dGTP and 2-oxo-dATP by exchanging the protonation state between Asp119 and Asp120 with higher pK(a) .

-	~~Authors~~:	+	Protonation states of Asp residues in the human Nudix hydrolase MTH1 contribute to its broad substrate recognition.,Nakamura T, Koga-Ogawa Y, Fujimiya K, Chirifu M, Goto M, Ikemizu S, Nakabeppu Y, Yamagata Y FEBS Lett. 2023 Mar 13. doi: 10.1002/1873-3468.14611. PMID:36914375<ref>PMID:36914375</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 8i1a" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Nakamura T]]
		+	[[Category: Yamagata Y]]

OCA at 05:24, 8 February 2023

OCA — Wed, 08 Feb 2023 05:24:08 GMT

←Older revision		Revision as of 05:24, 8 February 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8i1a is ON HOLD	+	The entry 8i1a is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "8i1a" [edit=sysop:move=sysop]

OCA — Wed, 18 Jan 2023 05:30:38 GMT

Protected "8i1a" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:30, 18 January 2023

OCA: New page: '''Unreleased structure''' The entry 8i1a is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 18 Jan 2023 05:30:36 GMT

New page: '''Unreleased structure''' The entry 8i1a is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8i1a is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]