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1iry

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Revision as of 00:18, 25 December 2014

Solution structure of the hMTH1, a nucleotide pool sanitization enzyme

Structural highlights

1iry is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	hMTH1 (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[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.^[1] ^[2] ^[3] ^[4] ^[5]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Oxygen radicals generated through normal cellular respiration processes can cause mutations in genomic and mitochondrial DNA. Human MTH1 hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-dGTP and 2-hydroxy-dATP, to monophosphates, thereby preventing the misincorporation of these oxidized nucleotides during replication. Here we present the solution structure of MTH1 solved by multidimensional heteronuclear NMR spectroscopy. The protein adopts a fold similar to that of Escherichia coli MutT, despite the low sequence similarity between these proteins outside the conserved Nudix motif. The substrate-binding pocket of MTH1, deduced from chemical shift perturbation experiments, is located at essentially the same position as in MutT; however, a pocket-forming helix is largely displaced in MTH1 (approximately 9 A) such that the shape of the pocket differs between the two proteins. Detailed analysis of the pocket-forming residues enabled us to identify Asn33 as one of the key residues in MTH1 for discriminating the oxidized form of purine, and mutation of this residue modifies the substrate specificity. We also show that MTH1 catalyzes hydrolysis of 8-oxo-dGTP through nucleophilic substitution of water at the beta-phosphate.

Structure of human MTH1, a Nudix family hydrolase that selectively degrades oxidized purine nucleoside triphosphates.,Mishima M, Sakai Y, Itoh N, Kamiya H, Furuichi M, Takahashi M, Yamagata Y, Iwai S, Nakabeppu Y, Shirakawa M J Biol Chem. 2004 Aug 6;279(32):33806-15. Epub 2004 May 7. PMID:15133035^[6]

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

References

↑ Fujikawa K, Kamiya H, Yakushiji H, Fujii Y, Nakabeppu Y, Kasai H. The oxidized forms of dATP are substrates for the human MutT homologue, the hMTH1 protein. J Biol Chem. 1999 Jun 25;274(26):18201-5. PMID:10373420
↑ Fujii Y, Shimokawa H, Sekiguchi M, Nakabeppu Y. Functional significance of the conserved residues for the 23-residue module among MTH1 and MutT family proteins. J Biol Chem. 1999 Dec 31;274(53):38251-9. PMID:10608900
↑ Fujikawa K, Kamiya H, Yakushiji H, Nakabeppu Y, Kasai H. Human MTH1 protein hydrolyzes the oxidized ribonucleotide, 2-hydroxy-ATP. Nucleic Acids Res. 2001 Jan 15;29(2):449-54. PMID:11139615
↑ Yoshimura D, Sakumi K, Ohno M, Sakai Y, Furuichi M, Iwai S, Nakabeppu Y. An oxidized purine nucleoside triphosphatase, MTH1, suppresses cell death caused by oxidative stress. J Biol Chem. 2003 Sep 26;278(39):37965-73. Epub 2003 Jul 10. PMID:12857738 doi:10.1074/jbc.M306201200
↑ Takagi Y, Setoyama D, Ito R, Kamiya H, Yamagata Y, Sekiguchi M. Human MTH3 (NUDT18) protein hydrolyzes oxidized forms of guanosine and deoxyguanosine diphosphates: comparison with MTH1 and MTH2. J Biol Chem. 2012 Jun 15;287(25):21541-9. doi: 10.1074/jbc.M112.363010. Epub 2012, May 3. PMID:22556419 doi:10.1074/jbc.M112.363010
↑ Mishima M, Sakai Y, Itoh N, Kamiya H, Furuichi M, Takahashi M, Yamagata Y, Iwai S, Nakabeppu Y, Shirakawa M. Structure of human MTH1, a Nudix family hydrolase that selectively degrades oxidized purine nucleoside triphosphates. J Biol Chem. 2004 Aug 6;279(32):33806-15. Epub 2004 May 7. PMID:15133035 doi:10.1074/jbc.M402393200

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1iry"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1iry]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IRY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1IRY FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">hMTH1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">hMTH1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1iry FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1iry OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1iry RCSB], [http://www.ebi.ac.uk/pdbsum/1iry PDBsum]</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=1iry FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1iry OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1iry RCSB], [http://www.ebi.ac.uk/pdbsum/1iry PDBsum]</span></td></tr>
-<table>
+</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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 32: / Line 34: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Itoh, N.]]
+[[Category: Itoh, N]]
-[[Category: Kamiya, H.]]
+[[Category: Kamiya, H]]
-[[Category: Mishima, M.]]
+[[Category: Mishima, M]]
-[[Category: Nakabeppu, Y.]]
+[[Category: Nakabeppu, Y]]
-[[Category: Sakai, Y.]]
+[[Category: Sakai, Y]]
-[[Category: Shirakawa, M.]]
+[[Category: Shirakawa, M]]
 [[Category: Hydrolase]]

1iry

From Proteopedia

Revision as of 00:18, 25 December 2014

Solution structure of the hMTH1, a nucleotide pool sanitization enzyme

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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