5ghj

From Proteopedia

(Difference between revisions)

Revision as of 16:40, 4 January 2017

Crystal structure of human MTH1(G2K mutant) in complex with 2-oxo-dATP

Structural highlights

5ghj is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	5ghi, 5ghm, 5ghn, 5gho, 5ghp, 5ghq
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

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.

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^[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
↑ Koga Y, Inazato M, Nakamura T, Hashikawa C, Chirifu M, Michi A, Yamashita T, Toma S, Kuniyasu A, Ikemizu S, Nakabeppu Y, Yamagata Y. Crystallization and preliminary X-ray analysis of human MTH1 with a homogeneous N-terminus. 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 doi:http://dx.doi.org/10.1107/S1744309112048002

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5ghj"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5ghj is ON HOLD  until Paper Publication
+==Crystal structure of human MTH1(G2K mutant) in complex with 2-oxo-dATP==
+<StructureSection load='5ghj' size='340' side='right' caption='[[5ghj]], [[Resolution|resolution]] 1.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5ghj]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GHJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5GHJ FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6U4:[[(2R,3S,5R)-5-(6-AZANYL-2-OXIDANYLIDENE-1H-PURIN-9-YL)-3-OXIDANYL-OXOLAN-2-YL]METHOXY-OXIDANYL-PHOSPHORYL]+PHOSPHONO+HYDROGEN+PHOSPHATE'>6U4</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]], [[5ghm|5ghm]], [[5ghn|5ghn]], [[5gho|5gho]], [[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=5ghj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ghj OCA], [http://pdbe.org/5ghj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ghj RCSB], [http://www.ebi.ac.uk/pdbsum/5ghj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ghj 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5ghj" 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]]

5ghj

From Proteopedia

Revision as of 16:40, 4 January 2017

Crystal structure of human MTH1(G2K mutant) in complex with 2-oxo-dATP

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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