1PM5

Crystal structure of wild type Lactococcus lactis Fpg complexed to a tetrahydrofuran containing DNA

1PM5 の概要

• エントリーDOI: 10.2210/pdb1pm5/pdb
• 関連するPDBエントリー: 1KFV 1NNJ
• 分子名称: DNA (5'-D(*CP*TP*CP*TP*TP*TP*(3DR)P*TP*TP*TP*CP*TP*CP*G)-3'), DNA (5'-D(*GP*CP*GP*AP*GP*AP*AP*AP*CP*AP*AP*AP*GP*A)-3'), Formamidopyrimidine-DNA glycosylase, ... (6 entities in total)
• 機能のキーワード: dna repair, fpg, mutm, abasic site, hydrolase-dna complex, hydrolase/dna
• 由来する生物種: Lactococcus lactis subsp. cremoris; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 39868.41

構造登録者

Pereira de Jesus-Tran, K.,Serre, L.,Zelwer, C.,Castaing, B. (登録日: 2003-06-10, 公開日: 2004-07-27, 最終更新日: 2023-08-16)

主引用文献

Pereira de Jesus, K.,Serre, L.,Zelwer, C.,Castaing, B.
Structural insights into abasic site for Fpg specific binding and catalysis: comparative high-resolution crystallographic studies of Fpg bound to various models of abasic site analogues-containing DNA.
Nucleic Acids Res., 33:5936-5944, 2005

PubMed Abstract: Fpg is a DNA glycosylase that recognizes and excises the mutagenic 8-oxoguanine (8-oxoG) and the potentially lethal formamidopyrimidic residues (Fapy). Fpg is also associated with an AP lyase activity which successively cleaves the abasic (AP) site at the 3' and 5' sides by betadelta-elimination. Here, we present the high-resolution crystal structures of the wild-type and the P1G defective mutant of Fpg from Lactococcus lactis bound to 14mer DNA duplexes containing either a tetrahydrofuran (THF) or 1,3-propanediol (Pr) AP site analogues. Structures show that THF is less extrahelical than Pr and its backbone C5'-C4'-C3' diverges significantly from those of Pr, rAP, 8-oxodG and FapydG. Clearly, the heterocyclic oxygen of THF is pushed back by the carboxylate of the strictly conserved E2 residue. We can propose that the ring-opened form of the damaged deoxyribose is the structure active form of the sugar for Fpg catalysis process. Both structural and functional data suggest that the first step of catalysis mediated by Fpg involves the expulsion of the O4' leaving group facilitated by general acid catalysis (involving E2), rather than the immediate cleavage of the N-glycosic bond of the damaged nucleoside.

PubMed: 16243784
DOI: 10.1093/nar/gki879

実験手法

X-RAY DIFFRACTION (1.95 Å)