4nrv: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
== Structural highlights == | == Structural highlights == | ||
<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> | <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" id="ligandDat"><scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</scene></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.601Å</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='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='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> | ||
</table> | </table> | ||
| Line 18: | Line 19: | ||
</div> | </div> | ||
<div class="pdbe-citations 4nrv" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4nrv" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Endonuclease 3D structures|Endonuclease 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
Latest revision as of 20:02, 20 September 2023
Crystal Structure of non-edited human NEIL1Crystal Structure of non-edited human NEIL1
Structural highlights
FunctionNEIL1_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 PubMedThe 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. See AlsoReferences
|
| ||||||||||||||||||