5itt: Difference between revisions

Revision as of 07:31, 3 June 2020

Crystal Structure of Human NEIL1 bound to duplex DNA containing THF

Structural highlights

5itt 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.
Ligands:	GOL
Related:	5itx, 5ity, 5itq, 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 bound to duplex DNA containing THF==
-<StructureSection load='5itt' size='340' side='right' caption='[[5itt]], [[Resolution|resolution]] 2.53&Aring;' scene=''>
+<StructureSection load='5itt' size='340' side='right'caption='[[5itt]], [[Resolution|resolution]] 2.53&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5itt]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ITT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ITT FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5itt]] 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=5ITT OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5ITT FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5itx|5itx]], [[5ity|5ity]], [[5itq|5itq]], [[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=5itt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5itt OCA], [http://pdbe.org/5itt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5itt RCSB], [http://www.ebi.ac.uk/pdbsum/5itt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5itt 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=5itt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5itt OCA], [http://pdbe.org/5itt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5itt RCSB], [http://www.ebi.ac.uk/pdbsum/5itt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5itt ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Gao, Y]]
 [[Category: Liu, M]]

5itt: Difference between revisions

Revision as of 07:31, 3 June 2020

Crystal Structure of Human NEIL1 bound to duplex DNA containing THF

Structural highlights

Function

Publication Abstract from PubMed

References

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