5itx: Difference between revisions

Revision as of 07:31, 3 June 2020

Crystal Structure of Human NEIL1(P2G R242K) bound to duplex DNA containing Thymine Glycol

Structural highlights

5itx is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:	CTG
Related:	5ity, 5itq, 5itt, 5itr, 5itu
Gene:	NEIL1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 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^[5]

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

References

↑ Takao M, Kanno S, Kobayashi K, Zhang QM, Yonei S, van der Horst GT, Yasui A. A back-up glycosylase in Nth1 knock-out mice is a functional Nei (endonuclease VIII) homologue. J Biol Chem. 2002 Nov 1;277(44):42205-13. Epub 2002 Aug 27. PMID:12200441 doi:https://dx.doi.org/10.1074/jbc.M206884200
↑ Bandaru V, Sunkara S, Wallace SS, Bond JP. A novel human DNA glycosylase that removes oxidative DNA damage and is homologous to Escherichia coli endonuclease VIII. DNA Repair (Amst). 2002 Jul 17;1(7):517-29. PMID:12509226
↑ Hazra TK, Izumi T, Boldogh I, Imhoff B, Kow YW, Jaruga P, Dizdaroglu M, Mitra S. Identification and characterization of a human DNA glycosylase for repair of modified bases in oxidatively damaged DNA. Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3523-8. PMID:11904416 doi:https://dx.doi.org/10.1073/pnas.062053799
↑ Dou H, Mitra S, Hazra TK. Repair of oxidized bases in DNA bubble structures by human DNA glycosylases NEIL1 and NEIL2. J Biol Chem. 2003 Dec 12;278(50):49679-84. Epub 2003 Sep 30. PMID:14522990 doi:https://dx.doi.org/10.1074/jbc.M308658200
↑ Zhu C, Lu L, Zhang J, Yue Z, Song J, Zong S, Liu M, Stovicek O, Gao YQ, Yi C. Tautomerization-dependent recognition and excision of oxidation damage in base-excision DNA repair. 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 doi:https://dx.doi.org/10.1073/pnas.1604591113

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Takao M, Kanno S, Kobayashi K, Zhang QM, Yonei S, van der Horst GT, Yasui A. A back-up glycosylase in Nth1 knock-out mice is a functional Nei (endonuclease VIII) homologue. J Biol Chem. 2002 Nov 1;277(44):42205-13. Epub 2002 Aug 27. PMID:12200441 doi:https://dx.doi.org/10.1074/jbc.M206884200

[2] Bandaru V, Sunkara S, Wallace SS, Bond JP. A novel human DNA glycosylase that removes oxidative DNA damage and is homologous to Escherichia coli endonuclease VIII. DNA Repair (Amst). 2002 Jul 17;1(7):517-29. PMID:12509226

[3] Hazra TK, Izumi T, Boldogh I, Imhoff B, Kow YW, Jaruga P, Dizdaroglu M, Mitra S. Identification and characterization of a human DNA glycosylase for repair of modified bases in oxidatively damaged DNA. Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3523-8. PMID:11904416 doi:https://dx.doi.org/10.1073/pnas.062053799

[4] Dou H, Mitra S, Hazra TK. Repair of oxidized bases in DNA bubble structures by human DNA glycosylases NEIL1 and NEIL2. J Biol Chem. 2003 Dec 12;278(50):49679-84. Epub 2003 Sep 30. PMID:14522990 doi:https://dx.doi.org/10.1074/jbc.M308658200

[5] Zhu C, Lu L, Zhang J, Yue Z, Song J, Zong S, Liu M, Stovicek O, Gao YQ, Yi C. Tautomerization-dependent recognition and excision of oxidation damage in base-excision DNA repair. 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 doi:https://dx.doi.org/10.1073/pnas.1604591113

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@@ Line 1: / Line 1: @@
 ==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]] 2.65&Aring;' scene=''>
+<StructureSection load='5itx' size='340' side='right'caption='[[5itx]], [[Resolution|resolution]] 2.65&Aring;' scene=''>
 == 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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ITX FirstGlance]. <br>
+<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>
 <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://oca.weizmann.ac.il/oca-docs/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>
+<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>
 == Function ==
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Gao, Y]]
 [[Category: Liu, M]]

5itx: Difference between revisions

Revision as of 07:31, 3 June 2020

Crystal Structure of Human NEIL1(P2G R242K) bound to duplex DNA containing Thymine Glycol

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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