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| | ==Crystal structure of mouse Endonuclease VIII-LIKE 3 (mNEIL3)== | | ==Crystal structure of mouse Endonuclease VIII-LIKE 3 (mNEIL3)== |
| - | <StructureSection load='3w0f' size='340' side='right' caption='[[3w0f]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='3w0f' size='340' side='right'caption='[[3w0f]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3w0f]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W0F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3W0F FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3w0f]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3W0F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3W0F FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mouse, Neil3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=3w0f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w0f OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3w0f RCSB], [http://www.ebi.ac.uk/pdbsum/3w0f PDBsum]</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=3w0f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w0f OCA], [https://pdbe.org/3w0f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3w0f RCSB], [https://www.ebi.ac.uk/pdbsum/3w0f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3w0f ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/NEIL3_MOUSE NEIL3_MOUSE] DNA glycosylase which prefers single-stranded DNA (ssDNA), or partially ssDNA structures such as bubble and fork structures, to double-stranded DNA (dsDNA). In vitro, displays strong glycosylase activity towards the hydantoin lesions spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh) in both ssDNA and dsDNA; also recognizes FapyA, FapyG, 5-OHU, 5-OHC, 5-OHMH, Tg and 8-oxoA lesions in ssDNA. No activity on 8-oxoG detected. Also shows weak DNA-(apurinic or apyrimidinic site) lyase activity. In vivo, appears to be the primary enzyme involved in removing Sp and Gh from ssDNA in neonatal tissues. Seems to be an important facilitator of cell proliferation in certain populations, for example neural stem/progenitor cells and tumor cells, suggesting a role in replication-associated DNA repair.<ref>PMID:20185759</ref> <ref>PMID:22065741</ref> <ref>PMID:22569481</ref> <ref>PMID:22959434</ref> <ref>PMID:23305905</ref> <ref>PMID:23313161</ref> |
| - | Endonuclease VIII-like 3 (Neil3) is a DNA glycosylase of the base excision repair pathway that protects cells from oxidative DNA damage by excising a broad spectrum of cytotoxic and mutagenic base lesions. Interestingly, Neil3 exhibits an unusual preference for DNA with single-stranded regions. Here, we report the 2.0 A crystal structure of a Neil3 enzyme. Although the glycosylase region of mouse Neil3 (MmuNeil3Delta324) exhibits the same overall fold as that of other Fpg/Nei proteins, it presents distinct structural features. First, MmuNeil3Delta324 lacks the alphaF-beta9/10 loop that caps the flipped-out 8-oxoG in bacterial Fpg, which is consistent with its inability to cleave 8-oxoguanine. Second, Neil3 not only lacks two of the three void-filling residues that stabilize the opposite strand, but it also harbors negatively charged residues that create an unfavorable electrostatic environment for the phosphate backbone of that strand. These structural features provide insight into the substrate specificity and marked preference of Neil3 for ssDNA.
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| - | Structural Characterization of a Mouse Ortholog of Human NEIL3 with a Marked Preference for Single-Stranded DNA.,Liu M, Imamura K, Averill AM, Wallace SS, Doublie S Structure. 2013 Feb 5;21(2):247-56. doi: 10.1016/j.str.2012.12.008. Epub 2013 Jan, 9. PMID:23313161<ref>PMID:23313161</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div> | + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
| - | [[Category: Averill, A M]] | + | [[Category: Averill AM]] |
| - | [[Category: Doublie, S]] | + | [[Category: Doublie S]] |
| - | [[Category: Imamura, K]] | + | [[Category: Imamura K]] |
| - | [[Category: Liu, M]] | + | [[Category: Liu M]] |
| - | [[Category: Wallace, S S]] | + | [[Category: Wallace SS]] |
| - | [[Category: Dna binding]]
| + | |
| - | [[Category: Helix two turns helix]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Zinc finger]]
| + | |
| Structural highlights
Function
NEIL3_MOUSE DNA glycosylase which prefers single-stranded DNA (ssDNA), or partially ssDNA structures such as bubble and fork structures, to double-stranded DNA (dsDNA). In vitro, displays strong glycosylase activity towards the hydantoin lesions spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh) in both ssDNA and dsDNA; also recognizes FapyA, FapyG, 5-OHU, 5-OHC, 5-OHMH, Tg and 8-oxoA lesions in ssDNA. No activity on 8-oxoG detected. Also shows weak DNA-(apurinic or apyrimidinic site) lyase activity. In vivo, appears to be the primary enzyme involved in removing Sp and Gh from ssDNA in neonatal tissues. Seems to be an important facilitator of cell proliferation in certain populations, for example neural stem/progenitor cells and tumor cells, suggesting a role in replication-associated DNA repair.[1] [2] [3] [4] [5] [6]
References
- ↑ Liu M, Bandaru V, Bond JP, Jaruga P, Zhao X, Christov PP, Burrows CJ, Rizzo CJ, Dizdaroglu M, Wallace SS. The mouse ortholog of NEIL3 is a functional DNA glycosylase in vitro and in vivo. Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):4925-30. doi:, 10.1073/pnas.0908307107. Epub 2010 Feb 25. PMID:20185759 doi:http://dx.doi.org/10.1073/pnas.0908307107
- ↑ Sejersted Y, Hildrestrand GA, Kunke D, Rolseth V, Krokeide SZ, Neurauter CG, Suganthan R, Atneosen-Asegg M, Fleming AM, Saugstad OD, Burrows CJ, Luna L, Bjoras M. Endonuclease VIII-like 3 (Neil3) DNA glycosylase promotes neurogenesis induced by hypoxia-ischemia. Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18802-7. doi:, 10.1073/pnas.1106880108. Epub 2011 Nov 7. PMID:22065741 doi:http://dx.doi.org/10.1073/pnas.1106880108
- ↑ Liu M, Bandaru V, Holmes A, Averill AM, Cannan W, Wallace SS. Expression and purification of active mouse and human NEIL3 proteins. Protein Expr Purif. 2012 Jul;84(1):130-9. doi: 10.1016/j.pep.2012.04.022. Epub, 2012 May 5. PMID:22569481 doi:http://dx.doi.org/10.1016/j.pep.2012.04.022
- ↑ Regnell CE, Hildrestrand GA, Sejersted Y, Medin T, Moldestad O, Rolseth V, Krokeide SZ, Suganthan R, Luna L, Bjoras M, Bergersen LH. Hippocampal adult neurogenesis is maintained by Neil3-dependent repair of oxidative DNA lesions in neural progenitor cells. Cell Rep. 2012 Sep 27;2(3):503-10. doi: 10.1016/j.celrep.2012.08.008. Epub 2012, Sep 6. PMID:22959434 doi:http://dx.doi.org/10.1016/j.celrep.2012.08.008
- ↑ Rolseth V, Krokeide SZ, Kunke D, Neurauter CG, Suganthan R, Sejersted Y, Hildrestrand GA, Bjoras M, Luna L. Loss of Neil3, the major DNA glycosylase activity for removal of hydantoins in single stranded DNA, reduces cellular proliferation and sensitizes cells to genotoxic stress. Biochim Biophys Acta. 2013 May;1833(5):1157-64. doi:, 10.1016/j.bbamcr.2012.12.024. Epub 2013 Jan 7. PMID:23305905 doi:http://dx.doi.org/10.1016/j.bbamcr.2012.12.024
- ↑ Liu M, Imamura K, Averill AM, Wallace SS, Doublie S. Structural Characterization of a Mouse Ortholog of Human NEIL3 with a Marked Preference for Single-Stranded DNA. Structure. 2013 Feb 5;21(2):247-56. doi: 10.1016/j.str.2012.12.008. Epub 2013 Jan, 9. PMID:23313161 doi:http://dx.doi.org/10.1016/j.str.2012.12.008
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