5itx: Difference between revisions
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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 [http:// | <table><tr><td colspan='2'>[[5itx]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://proteopedia.org/fgij/fg.htm?mol=5ITX FirstGlance]. <br> | ||
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CTG:(5R,6S)-5,6-DIHYDRO-5,6-DIHYDROXYTHYMIDINE-5-MONOPHOSPHATE'>CTG</scene></td></tr> | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CTG:(5R,6S)-5,6-DIHYDRO-5,6-DIHYDROXYTHYMIDINE-5-MONOPHOSPHATE'>CTG</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ity|5ity]], [[5itq|5itq]], [[5itt|5itt]], [[5itr|5itr]], [[5itu|5itu]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ity|5ity]], [[5itq|5itq]], [[5itt|5itt]], [[5itr|5itr]], [[5itu|5itu]]</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NEIL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5itx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5itx OCA], [http://pdbe.org/5itx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5itx RCSB], [http://www.ebi.ac.uk/pdbsum/5itx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5itx ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | == Function == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Gao, Y]] | [[Category: Gao, Y]] | ||
[[Category: Liu, M]] | [[Category: Liu, M]] | ||
Revision as of 10:31, 3 June 2020
Crystal Structure of Human NEIL1(P2G R242K) bound to duplex DNA containing Thymine GlycolCrystal Structure of Human NEIL1(P2G R242K) bound to duplex DNA containing Thymine Glycol
Structural highlights
Function[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.[1] [2] [3] [4] Publication Abstract from PubMedNEIL1 (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[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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