1pjj
From Proteopedia
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Complex between the Lactococcus lactis Fpg and an abasic site containing DNA.
Overview
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.
About this Structure
1PJJ is a Single protein structure of sequence from Lactococcus lactis with ZN and GOL as ligands. Active as DNA-formamidopyrimidine glycosylase, with EC number 3.2.2.23 Full crystallographic information is available from OCA.
Reference
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., Pereira de Jesus K, Serre L, Zelwer C, Castaing B, Nucleic Acids Res. 2005 Oct 20;33(18):5936-44. Print 2005. PMID:16243784
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