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4nrv

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Revision as of 08:35, 18 January 2023

Crystal Structure of non-edited human NEIL1

Structural highlights

4nrv is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
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

The repair of free-radical oxidative DNA damage is carried out by lesion-specific DNA glycosylases as the first step of the highly conserved base excision repair (BER) pathway. In humans, three orthologs of the prototypical endonuclease VIII (Nei), the Nei-like NEIL1-3 enzymes are involved in the repair of oxidized DNA lesions. In recent years, several genome and cancer single-nucleotide polymorphic variants of the NEIL1 glycosylase have been identified. In this study we characterized four variants of human NEIL1: S82C, G83D, P208S, and DeltaE28, and tested their ability to excise pyrimidine-derived lesions such as thymine glycol (Tg), 5-hydroxyuracil (5-OHU), and dihydrouracil (DHU) and the purine-derived guanidinohydantoin (Gh), spiroiminodihydantoin 1 (Sp1), and methylated 2,6-diamino-4-hydroxy-5-formamidopyrimidine (MeFapyG). The P208S variant has near wild-type activity on all substrates tested. The S82C and DeltaE28 variants exhibit decreased Tg excision compared to wild-type. G83D displays little to no activity with any of the substrates tested, with the exception of Gh and Sp1. Human NEIL1 is known to undergo editing whereby the lysine at position 242 is recoded into an arginine. The non-edited form of NEIL1 is more efficient at cleaving Tg than the R242 form, but the G83D variant does not cleave Tg regardless of the edited status of NEIL1. The corresponding G86D variant in Mimivirus Nei1 similarly lacks glycosylase activity. A structure of a G86D-DNA complex reveals a rearrangement in the beta4/5 loop comprising Leu84, the highly-conserved void-filling residue, thereby providing a structural rationale for the decreased glycosylase activity of the glycine to aspartate variant.

Genome and cancer single nucleotide polymorphisms of the human NEIL1 DNA glycosylase: Activity, structure, and the effect of editing.,Prakash A, Carroll BL, Sweasy JB, Wallace SS, Doublie S DNA Repair (Amst). 2014 Feb;14:17-26. doi: 10.1016/j.dnarep.2013.12.003. Epub, 2013 Dec 29. PMID:24382305^[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:http://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:http://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:http://dx.doi.org/10.1074/jbc.M308658200
↑ Prakash A, Carroll BL, Sweasy JB, Wallace SS, Doublie S. Genome and cancer single nucleotide polymorphisms of the human NEIL1 DNA glycosylase: Activity, structure, and the effect of editing. DNA Repair (Amst). 2014 Feb;14:17-26. doi: 10.1016/j.dnarep.2013.12.003. Epub, 2013 Dec 29. PMID:24382305 doi:http://dx.doi.org/10.1016/j.dnarep.2013.12.003

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4nrv"

Categories: Homo sapiens | Large Structures | Doublie S | Prakash A

@@ Line 1: / Line 1: @@
 ==Crystal Structure of non-edited human NEIL1==
-<StructureSection load='4nrv' size='340' side='right' caption='[[4nrv]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
+<StructureSection load='4nrv' size='340' side='right'caption='[[4nrv]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4nrv]] is a 1 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=4NRV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NRV FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4nrv]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NRV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4NRV FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nrw|4nrw]]</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=4nrv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nrv OCA], [https://pdbe.org/4nrv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4nrv RCSB], [https://www.ebi.ac.uk/pdbsum/4nrv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4nrv ProSAT]</span></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Endonuclease VIII (nei) 1, 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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4nrv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nrv OCA], [http://pdbe.org/4nrv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4nrv RCSB], [http://www.ebi.ac.uk/pdbsum/4nrv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4nrv ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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>
+[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 ==
@@ Line 24: / Line 22: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Doublie, S]]
+[[Category: Large Structures]]
-[[Category: Prakash, A]]
+[[Category: Doublie S]]
-[[Category: Dna glycosylase]]
+[[Category: Prakash A]]
-[[Category: Helix two-turns helix motif]]
-[[Category: Hydrolase]]
-[[Category: Lyase]]
-[[Category: Zincless finger domain]]

4nrv

From Proteopedia

Revision as of 08:35, 18 January 2023

Crystal Structure of non-edited human NEIL1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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