3VK8

Crystal structure of DNA-glycosylase bound to DNA containing Thymine glycol

3VK8 の概要

• エントリーDOI: 10.2210/pdb3vk8/pdb
• 関連するPDBエントリー: 3A46 3VK7
• 分子名称: Probable formamidopyrimidine-DNA glycosylase, DNA (5'-D(*GP*TP*AP*GP*AP*CP*CP*TP*GP*GP*AP*CP*G)-3'), DNA (5'-D(*CP*GP*TP*CP*CP*AP*(CTG)P*GP*TP*CP*TP*AP*C)-3'), ... (5 entities in total)
• 機能のキーワード: dna glycosylase, hneil1 ortholog, dna lesion, thymine glycol, zincless finger, dna binding, hydrolase-dna complex, hydrolase/dna
• 由来する生物種: Acanthamoeba polyphaga mimivirus (APMV)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 85161.20

構造登録者

Imamura, K.,Averill, A.,Wallace, S.S.,Doublie, S. (登録日: 2011-11-10, 公開日: 2011-12-14, 最終更新日: 2024-03-20)

主引用文献

Imamura, K.,Averill, A.,Wallace, S.S.,Doublie, S.
Structural characterization of viral ortholog of human DNA glycosylase NEIL1 bound to thymine glycol or 5-hydroxyuracil-containing DNA
J.Biol.Chem., 287:4288-4298, 2012

PubMed Abstract: Thymine glycol (Tg) and 5-hydroxyuracil (5-OHU) are common oxidized products of pyrimidines, which are recognized and cleaved by two DNA glycosylases of the base excision repair pathway, endonuclease III (Nth) and endonuclease VIII (Nei). Although there are several structures of Nei enzymes unliganded or bound to an abasic (apurinic or apyrimidinic) site, until now there was no structure of an Nei bound to a DNA lesion. Mimivirus Nei1 (MvNei1) is an ortholog of human NEIL1, which was previously crystallized bound to DNA containing an apurinic site (Imamura, K., Wallace, S. S., and Doublié, S. (2009) J. Biol. Chem. 284, 26174-26183). Here, we present two crystal structures of MvNei1 bound to two oxidized pyrimidines, Tg and 5-OHU. Both lesions are flipped out from the DNA helix. Tg is in the anti conformation, whereas 5-OHU adopts both anti and syn conformations in the glycosylase active site. Only two protein side chains (Glu-6 and Tyr-253) are within hydrogen-bonding contact with either damaged base, and mutating these residues did not markedly affect the glycosylase activity. This finding suggests that lesion recognition by Nei occurs before the damaged base flips into the glycosylase active site.

PubMed: 22170059
DOI: 10.1074/jbc.M111.315309

実験手法

X-RAY DIFFRACTION (2 Å)