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PDBsum entry 1tdz

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Top Page protein dna_rna ligands metals links
Hydrolase/DNA PDB id
1tdz
Jmol
Contents
Protein chain
265 a.a. *
DNA/RNA
Ligands
GOL
Metals
_ZN
Waters ×431
* Residue conservation analysis

References listed in PDB file
Key reference
Title Structural basis for the recognition of the fapydg lesion (2,6-Diamino-4-Hydroxy-5-Formamidopyrimidine) by formamidopyrimidine-Dna glycosylase.
Authors F.Coste, M.Ober, T.Carell, S.Boiteux, C.Zelwer, B.Castaing.
Ref. J Biol Chem, 2004, 279, 44074-44083. [DOI no: 10.1074/jbc.M405928200]
PubMed id 15249553
Abstract
Formamidopyrimidine-DNA glycosylase (Fpg) is a DNA repair enzyme that excises oxidized purines such as 7,8-dihydro-8-oxoguanine (8-oxoG) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) from damaged DNA. Here, we report the crystal structure of the Fpg protein from Lactococcus lactis (LlFpg) bound to a carbocyclic FapydG (cFapydG)-containing DNA. The structure reveals that Fpg stabilizes the cFapydG nucleoside into an extrahelical conformation inside its substrate binding pocket. In contrast to the recognition of the 8-oxodG lesion, which is bound with the glycosidic bond in a syn conformation, the cFapydG lesion displays in the complex an anti conformation. Furthermore, Fpg establishes interactions with all the functional groups of the FapyG base lesion, which can be classified in two categories: (i) those specifying a purine-derived lesion (here a guanine) involved in the Watson-Crick face recognition of the lesion and probably contributing to an optimal orientation of the pyrimidine ring moiety in the binding pocket and (ii) those specifying the imidazole ring-opened moiety of FapyG and probably participating also in the rotameric selection of the FapydG nucleobase. These interactions involve strictly conserved Fpg residues and structural water molecules mediated interactions. The significant differences between the Fpg recognition modes of 8-oxodG and FapydG provide new insights into the Fpg substrate specificity.
Figure 4.
FIG. 4. Interactions between the extrahelical cFapydG and Fpg residues inside the active site binding pocket. A, schematic representation of Fpg/DNA contacts at the target site. Amino acid residues of LlFpg involved in the recognition are shown in red and the DNA are shown in blue. C, the cytosine opposite cFapydG (G*). p0 and p-1 indicate the phosphate groups bordering the lesion. Small green circles represent the water-mediated interactions. Black dashed lines represent hydrogen bond interactions. B, stereoviews of the cFapydG recognition complex active site. The C- backbone of Fpg is in yellow, main chains and side chains of indicated Fpg residues are in yellow and pink, respectively. Covalent links are indicated by ball-and-sticks representation. Carbons of DNA are shown in gray, oxygen atoms in red, nitrogen atoms in blue, phosphate atoms in dark magenta, and sulfur atoms in orange. The water molecules (wat) mediating interactions between Fpg residues and the cFapydG functional groups are indicated by small red spheres. Inferred hydrogen bonds are shown as orange dashed lines. C, distances between hydrogen bond donors and acceptors indicated in B.
Figure 6.
FIG. 6. Superimposition of cFapydG (anti) and 8-oxodG (syn) nucleobases in the extrahelical base binding pocket of Fpg. Carbons of cFapydG and 8-oxodG are shown as gray and green spheres, respectively. The chemical mutation of the heterocycle oxygen (O4') of the deoxyribose in the -CH[2] group in the cyclopentane of cFapydG is indicated as the 6' position.
The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 44074-44083) copyright 2004.
PROCHECK
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