PDBsum entry 1f6c

DNA

PDB id

1f6c

Contents

			DNA/RNA

			Ligands

					SPM ×2

			Waters ×16

References listed in PDB file

Key reference

Title

The extended and eccentric e-Dna structure induced by cytosine methylation or bromination.

Authors

J.M.Vargason, B.F.Eichman, P.S.Ho.

Ref.

Nat Struct Biol, 2000, 7, 758-761. [DOI no: 10.1038/78985]

PubMed id

10966645

Abstract

Cytosine methylation or bromination of the DNA sequence d(GGCGCC)2 is shown here to induce a novel extended and eccentric double helix, which we call E-DNA. Like B-DNA, E-DNA has a long helical rise and bases perpendicular to the helix axis. However, the 3'-endo sugar conformation gives the characteristic deep major groove and shallow minor groove of A-DNA. Also, if allowed to crystallize for a period of time longer than that yielding E-DNA, the methylated sequence forms standard A-DNA, suggesting that E-DNA is a kinetically trapped intermediate in the transition to A-DNA. Thus, the structures presented here chart a crystallographic pathway from B-DNA to A-DNA through the E-DNA intermediate in a single sequence. The E-DNA surface is highly accessible to solvent, with waters in the major groove sitting on exposed faces of the stacked nucleotides. We suggest that the geometry of the waters and the stacked base pairs would promote the spontaneous deamination of 5-methylcytosine in the transition mutation of dm5C-dG to dT-dA base pairs.



	Figure 2. Figure 2. Electron density maps showing stereo views looking into the major grooves of the B-, E-, and A-DNA structures. a, d(GGCGCC)[2] with Co3+ (purple sphere) as B-DNA; b, d(GGCGm5CC)[2] as E-DNA; c, d(GGCGm5CC)[2] as A-DNA. The 2F[o] - F[c] maps are contoured at 1 . This figure was rendered with Raster3D^23.		Figure 3. Figure 3. Waters in the CpG dinucleotides of B-DNA and E-DNA. a, Stereo view of waters (gold spheres) hydrogen bonded (broken lines) to the guanine at the CpG steps in d(GGCGCC)[2] as B-DNA, and in d(GGCGm5CC)[2] and d(GGCGBr5CC)[2] as E-DNA. The waters are overlaid relative to the guanine N7 nitrogen of an average structure built from three unique CpG steps found in each conformation (the C4 carbon of the cytosine base is colored black). b, Mechanism for the spontaneous deamination of cytosine to uracil24. The nucleophilic attack of a water molecule at the C4 carbon forms a hemiaminal intermediate. Release of ammonia results in a tautomer, which subsequently rearranges to uracil. c, Model of the hemiaminal intermediate in B-DNA and E-DNA. The hemiaminal intermediate at the CpG step was modeled by adding a hydroxyl group to the C4 carbon (colored black) of the cytosine base, followed by geometry optimization using the AMBER25 force field as implemented in the program InsightII (Biosym/MSI). The starting positions of the waters and the starting cytosine base are shown as transparent overlays.

	Headers