1B5K: 3,n4-etheno-2'-deoxycytidine Opposite Thymidine In An 11-mer Duplex, Solution Structure From Nmr And Molecular Dynamics

The exocyclic 3,N4-etheno-2'-deoxycytidine adduct was incorporated at the center of the oligodeoxynucleotide duplex d(C-G-T-A-C-epsilon C-C-A-T-G-C).d (G-C-A-T-G-T-G-T-A-C-G), and its solution structure was analyzed using high-resolution proton NMR spectroscopy and molecular dynamics simulations. The experimental data indicate that the oligodeoxynucleotide duplex adopts a right-handed helical structure with sugar puckers in the C2'-endo/C3'-exo range and Watson-Crick hydrogen bond alignments for all base pairs. NOE connectivities established a syn orientation for the glycosidic torsion angle of the exocyclic adduct. Restrained molecular dynamics simulations, using the full relaxation matrix approach, produced a three-dimensional model in agreement with the experimental data. The structure shows only minor perturbations in the sugar-phosphate backbone and a 27 degrees bend of the helical axis at the lesion site. On the refined model a well-formed hydrogen bond between T (N3H) and epsilon C(N4) stabilizes the epsilon C(syn).T(anti) base pair alignment, reflecting the preference of the adduct for the syn orientation. Furthermore, the epsilon C(syn).T(anti) base pair stacks with flanking base pairs. We discuss a correlation between the mutagenic properties of the adduct and the three-dimensional structure of the epsilon C.dA and epsilon C.T duplexes.
PDB ID: 1B5KDownload
MMDB ID: 48072
PDB Deposition Date: 1999/1/7
Updated in MMDB: 2007/10
Experimental Method:
solution nmr
Biological Unit for 1B5K: dimeric; determined by author
Molecular Components in 1B5K
Label Count Molecule
Nucleotides(2 molecules)
DNA (5'-d(*cp*gp*tp*ap*cp*edcp*cp*ap*tp*gp*c)-3')
Molecule annotation
DNA (5'-d(*gp*cp*ap*tp*gp*tp*gp*tp*ap*cp*g)-3')
Molecule annotation
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