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| | <StructureSection load='6fl4' size='340' side='right'caption='[[6fl4]], [[Resolution|resolution]] 1.60Å' scene=''> | | <StructureSection load='6fl4' size='340' side='right'caption='[[6fl4]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6fl4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Arath Arath]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FL4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FL4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6fl4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Arabidopsis_thaliana Arabidopsis thaliana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FL4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FL4 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=MG:MAGNESIUM+ION'>MG</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]] 1.6Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NUDT1, NUDX1, At1g68760, F14K14.13 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=3702 ARATH])</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=MG:MAGNESIUM+ION'>MG</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=6fl4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fl4 OCA], [https://pdbe.org/6fl4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fl4 RCSB], [https://www.ebi.ac.uk/pdbsum/6fl4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fl4 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=6fl4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fl4 OCA], [https://pdbe.org/6fl4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fl4 RCSB], [https://www.ebi.ac.uk/pdbsum/6fl4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fl4 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/NUDT1_ARATH NUDT1_ARATH]] Mediates the hydrolysis of some nucleoside diphosphate derivatives. Its substrate specificity is unclear. In vitro, it can use NTP, dNTP, 8-oxo-GTP, 8-oxo-dGTP, dGTP, dATP, dTTP or dihydroneopterin triphosphate (DHNTP) as substrate. Has some NADH pyrophosphatase activity in vitro; however, such activity may not be relevant in vivo due to the high concentration of manganese used during the experiments. Plays an important role in protection against oxidative DNA and RNA damage by removing oxidatively damaged form of guanine.<ref>PMID:15611104</ref> <ref>PMID:15878881</ref> <ref>PMID:17804481</ref>
| + | [https://www.uniprot.org/uniprot/NUDT1_ARATH NUDT1_ARATH] Mediates the hydrolysis of some nucleoside diphosphate derivatives. Its substrate specificity is unclear. In vitro, it can use NTP, dNTP, 8-oxo-GTP, 8-oxo-dGTP, dGTP, dATP, dTTP or dihydroneopterin triphosphate (DHNTP) as substrate. Has some NADH pyrophosphatase activity in vitro; however, such activity may not be relevant in vivo due to the high concentration of manganese used during the experiments. Plays an important role in protection against oxidative DNA and RNA damage by removing oxidatively damaged form of guanine.<ref>PMID:15611104</ref> <ref>PMID:15878881</ref> <ref>PMID:17804481</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: Arath]] | + | [[Category: Arabidopsis thaliana]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Carter, M]] | + | [[Category: Carter M]] |
| - | [[Category: Helleday, T]] | + | [[Category: Helleday T]] |
| - | [[Category: Jemth, A S]] | + | [[Category: Jemth AS]] |
| - | [[Category: Scaletti-Hutchinson, E]] | + | [[Category: Scaletti-Hutchinson E]] |
| - | [[Category: Stenmark, P]] | + | [[Category: Stenmark P]] |
| - | [[Category: 8-oxo-dgtp]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Function
NUDT1_ARATH Mediates the hydrolysis of some nucleoside diphosphate derivatives. Its substrate specificity is unclear. In vitro, it can use NTP, dNTP, 8-oxo-GTP, 8-oxo-dGTP, dGTP, dATP, dTTP or dihydroneopterin triphosphate (DHNTP) as substrate. Has some NADH pyrophosphatase activity in vitro; however, such activity may not be relevant in vivo due to the high concentration of manganese used during the experiments. Plays an important role in protection against oxidative DNA and RNA damage by removing oxidatively damaged form of guanine.[1] [2] [3]
Publication Abstract from PubMed
Arabidopsis thaliana NUDT1 (AtNUDT1) belongs to the Nudix family of proteins, which have a diverse range of substrates, including oxidized nucleotides such as 8-oxo-dGTP. The hydrolysis of oxidized dNTPs is highly important as it prevents their incorporation into DNA, thus preventing mutations and DNA damage. AtNUDT1 is the sole Nudix enzyme from A. thaliana shown to have activity against 8-oxo-dGTP. We present the structure of AtNUDT1 in complex with 8-oxo-dGTP. Structural comparison with bacterial and human homologues reveals a conserved overall fold. Analysis of the 8-oxo-dGTP binding mode shows that the residues Asn76 and Ser89 interact with the O8 atom of the substrate, a feature not observed in structures of protein homologues solved to date. Kinetic analysis of wild-type and mutant AtNUDT1 confirmed that these active site residues influence 8-oxo-dGTP hydrolysis. A recent study showed that AtNUDT1 is also able to hydrolyze terpene compounds. The diversity of reactions catalyzed by AtNUDT1 suggests that this Nudix enzyme from higher plants has evolved in a manner distinct to those from other organisms.
Crystal Structure and Substrate Specificity of the 8-oxo-dGTP Hydrolase NUDT1 from Arabidopsis thaliana.,Jemth AS, Scaletti E, Carter M, Helleday T, Stenmark P Biochemistry. 2019 Feb 19;58(7):887-899. doi: 10.1021/acs.biochem.8b00950. Epub, 2019 Jan 16. PMID:30614695[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Klaus SM, Wegkamp A, Sybesma W, Hugenholtz J, Gregory JF 3rd, Hanson AD. A nudix enzyme removes pyrophosphate from dihydroneopterin triphosphate in the folate synthesis pathway of bacteria and plants. J Biol Chem. 2005 Feb 18;280(7):5274-80. Epub 2004 Dec 16. PMID:15611104 doi:http://dx.doi.org/M413759200
- ↑ Ogawa T, Ueda Y, Yoshimura K, Shigeoka S. Comprehensive analysis of cytosolic Nudix hydrolases in Arabidopsis thaliana. J Biol Chem. 2005 Jul 1;280(26):25277-83. Epub 2005 May 5. PMID:15878881 doi:http://dx.doi.org/M503536200
- ↑ Yoshimura K, Ogawa T, Ueda Y, Shigeoka S. AtNUDX1, an 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate pyrophosphohydrolase, is responsible for eliminating oxidized nucleotides in Arabidopsis. Plant Cell Physiol. 2007 Oct;48(10):1438-49. Epub 2007 Sep 5. PMID:17804481 doi:http://dx.doi.org/10.1093/pcp/pcm112
- ↑ Jemth AS, Scaletti E, Carter M, Helleday T, Stenmark P. Crystal Structure and Substrate Specificity of the 8-oxo-dGTP Hydrolase NUDT1 from Arabidopsis thaliana. Biochemistry. 2019 Feb 19;58(7):887-899. doi: 10.1021/acs.biochem.8b00950. Epub, 2019 Jan 16. PMID:30614695 doi:http://dx.doi.org/10.1021/acs.biochem.8b00950
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