5itx
From Proteopedia
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==Crystal Structure of Human NEIL1(P2G R242K) bound to duplex DNA containing Thymine Glycol== | ==Crystal Structure of Human NEIL1(P2G R242K) bound to duplex DNA containing Thymine Glycol== | ||
| - | <StructureSection load='5itx' size='340' side='right' caption='[[5itx]], [[Resolution|resolution]] 2.65Å' scene=''> | + | <StructureSection load='5itx' size='340' side='right'caption='[[5itx]], [[Resolution|resolution]] 2.65Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5itx]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ITX OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[5itx]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Unidentified Unidentified]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ITX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ITX FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.65Å</td></tr> |
| - | <tr id=' | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CTG:(5R,6S)-5,6-DIHYDRO-5,6-DIHYDROXYTHYMIDINE-5-MONOPHOSPHATE'>CTG</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5itx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5itx OCA], [https://pdbe.org/5itx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5itx RCSB], [https://www.ebi.ac.uk/pdbsum/5itx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5itx ProSAT]</span></td></tr> |
</table> | </table> | ||
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/NEIL1_HUMAN NEIL1_HUMAN] Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. Acts as DNA glycosylase that recognizes and removes damaged bases. Has a preference for oxidized pyrimidines, such as thymine glycol, formamidopyrimidine (Fapy) and 5-hydroxyuracil. Has marginal activity towards 8-oxoguanine. Has AP (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA strand. Cleaves the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates. Has DNA glycosylase/lyase activity towards mismatched uracil and thymine, in particular in U:C and T:C mismatches.<ref>PMID:12200441</ref> <ref>PMID:12509226</ref> <ref>PMID:11904416</ref> <ref>PMID:14522990</ref> |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | NEIL1 (Nei-like 1) is a DNA repair glycosylase guarding the mammalian genome against oxidized DNA bases. As the first enzymes in the base-excision repair pathway, glycosylases must recognize the cognate substrates and catalyze their excision. Here we present crystal structures of human NEIL1 bound to a range of duplex DNA. Together with computational and biochemical analyses, our results suggest that NEIL1 promotes tautomerization of thymine glycol (Tg)-a preferred substrate-for optimal binding in its active site. Moreover, this tautomerization event also facilitates NEIL1-catalyzed Tg excision. To our knowledge, the present example represents the first documented case of enzyme-promoted tautomerization for efficient substrate recognition and catalysis in an enzyme-catalyzed reaction. | ||
| + | |||
| + | Tautomerization-dependent recognition and excision of oxidation damage in base-excision DNA repair.,Zhu C, Lu L, Zhang J, Yue Z, Song J, Zong S, Liu M, Stovicek O, Gao YQ, Yi C Proc Natl Acad Sci U S A. 2016 Jul 12;113(28):7792-7. doi:, 10.1073/pnas.1604591113. Epub 2016 Jun 27. PMID:27354518<ref>PMID:27354518</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5itx" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Endonuclease 3D structures|Endonuclease 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: Gao | + | [[Category: Homo sapiens]] |
| - | [[Category: Liu | + | [[Category: Large Structures]] |
| - | [[Category: Lu | + | [[Category: Unidentified]] |
| - | [[Category: Song | + | [[Category: Gao Y]] |
| - | [[Category: Stovicek | + | [[Category: Liu M]] |
| - | [[Category: Yi | + | [[Category: Lu L]] |
| - | [[Category: Yue | + | [[Category: Song J]] |
| - | [[Category: Zhang | + | [[Category: Stovicek O]] |
| - | [[Category: Zhu | + | [[Category: Yi C]] |
| - | [[Category: Zong | + | [[Category: Yue Z]] |
| - | + | [[Category: Zhang J]] | |
| - | + | [[Category: Zhu C]] | |
| + | [[Category: Zong S]] | ||
Current revision
Crystal Structure of Human NEIL1(P2G R242K) bound to duplex DNA containing Thymine Glycol
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Categories: Homo sapiens | Large Structures | Unidentified | Gao Y | Liu M | Lu L | Song J | Stovicek O | Yi C | Yue Z | Zhang J | Zhu C | Zong S
