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5bon

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Revision as of 16:11, 17 May 2017

Crystal structure of human Nudt15 (MTH2)

Structural highlights

5bon is a 8 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Activity:	8-oxo-dGTP diphosphatase, with EC number 3.6.1.55
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[NUD15_HUMAN] Mediates the hydrolysis of some nucleoside diphosphate derivatives. Can degrade 8-oxo-dGTP in vitro, suggesting that it may remove an oxidatively damaged form of guanine (7,8-dihydro-8-oxoguanine) from DNA and the nucleotide pool, thereby preventing misincorporation of 8-oxo-dGTP into DNA thus preventing A:T to C:G transversions. Its substrate specificity in vivo however remains unclear (By similarity). May have a role in DNA synthesis and cell cycle progression through the interaction with PCNA.^[1] ^[2]

Publication Abstract from PubMed

Deregulated redox metabolism in cancer leads to oxidative damage to cellular components including deoxyribonucleoside triphosphates (dNTPs). Targeting dNTP pool sanitizing enzymes, such as MTH1, is a highly promising anticancer strategy. The MTH2 protein, known as NUDT15, is described as the second human homologue of bacterial MutT with 8-oxo-dGTPase activity. We present the first NUDT15 crystal structure and demonstrate that NUDT15 prefers other nucleotide substrates over 8-oxo-dGTP. Key structural features are identified that explain different substrate preferences for NUDT15 and MTH1. We find that depletion of NUDT15 has no effect on incorporation of 8-oxo-dGTP into DNA and does not impact cancer cell survival in cell lines tested. NUDT17 and NUDT18 were also profiled and found to have far less activity than MTH1 against oxidized nucleotides. We show that NUDT15 is not a biologically relevant 8-oxo-dGTPase, and that MTH1 is the most prominent sanitizer of the cellular dNTP pool known to date.

Crystal structure, biochemical and cellular activities demonstrate separate functions of MTH1 and MTH2.,Carter M, Jemth AS, Hagenkort A, Page BD, Gustafsson R, Griese JJ, Gad H, Valerie NC, Desroses M, Bostrom J, Warpman Berglund U, Helleday T, Stenmark P Nat Commun. 2015 Aug 4;6:7871. doi: 10.1038/ncomms8871. PMID:26238318^[3]

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

References

↑ Yu Y, Cai JP, Tu B, Wu L, Zhao Y, Liu X, Li L, McNutt MA, Feng J, He Q, Yang Y, Wang H, Sekiguchi M, Zhu WG. Proliferating cell nuclear antigen is protected from degradation by forming a complex with MutT Homolog2. J Biol Chem. 2009 Jul 17;284(29):19310-20. doi: 10.1074/jbc.M109.015289. Epub, 2009 May 6. PMID:19419956 doi:http://dx.doi.org/10.1074/jbc.M109.015289
↑ 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
↑ Carter M, Jemth AS, Hagenkort A, Page BD, Gustafsson R, Griese JJ, Gad H, Valerie NC, Desroses M, Bostrom J, Warpman Berglund U, Helleday T, Stenmark P. Crystal structure, biochemical and cellular activities demonstrate separate functions of MTH1 and MTH2. Nat Commun. 2015 Aug 4;6:7871. doi: 10.1038/ncomms8871. PMID:26238318 doi:http://dx.doi.org/10.1038/ncomms8871

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/5bon"

@@ Line 1: / Line 1: @@
 ==Crystal structure of human Nudt15 (MTH2)==
 <StructureSection load='5bon' size='340' side='right' caption='[[5bon]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/8-oxo-dGTP_diphosphatase 8-oxo-dGTP diphosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.1.55 3.6.1.55] </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=5bon FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bon OCA], [http://www.rcsb.org/pdb/explore.do?structureId=5bon RCSB], [http://www.ebi.ac.uk/pdbsum/5bon 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=5bon FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bon OCA], [http://pdbe.org/5bon PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bon RCSB], [http://www.ebi.ac.uk/pdbsum/5bon PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5bon ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 5bon" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

5bon

From Proteopedia

Revision as of 16:11, 17 May 2017

Crystal structure of human Nudt15 (MTH2)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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