2KD9

Solution Structure of DNA Containing Alpha-OH-PdG: the Mutagenic Adduct Produced by Acrolein

Summary for 2KD9

• Entry DOI: 10.2210/pdb2kd9/pdb
• Related: 2KDA
• Descriptor: 5'-D(*CP*GP*TP*AP*CP*(63G)P*CP*AP*TP*GP*C)-3', 5'-D(*GP*CP*AP*TP*GP*CP*GP*TP*AP*CP*G)-3' (2 entities in total)
• Functional Keywords: acrolein lesions, dna damaged, dna structure, exocyclic, propano-dg lesions, dna
• Total number of polymer chains: 2
• Total formula weight: 6764.46

Authors

de los Santos, C.,Zaliznyak, T.,Johnson, F.,Bonala, R.,Attaluri, S. (deposition date: 2009-01-05, release date: 2009-04-21, Last modification date: 2024-05-22)

Primary citation

Zaliznyak, T.,Bonala, R.,Attaluri, S.,Johnson, F.,de los Santos, C.
Solution structure of DNA containing alpha-OH-PdG: the mutagenic adduct produced by acrolein.
Nucleic Acids Res., 37:2153-2163, 2009

PubMed Abstract: Acrolein is a cell metabolic product and a main component of cigarette smoke. Its reaction with DNA produces two guanine lesions gamma-OH-PdG, a major adduct that is nonmutagenic in mammalian cells, and the positional isomer alpha-OH-PdG. We describe here the solution structure of a short DNA duplex containing a single alpha-OH-PdG lesion, as determined by solution NMR spectroscopy and restrained molecular dynamics simulations. The spectroscopic data show a mostly regular right-handed helix, locally perturbed at its center by the presence of the lesion. All undamaged residues of the duplex are in anti orientation, forming standard Watson-Crick base-pair alignments. Duplication of proton signals near the damaged site differentiates two enantiomeric duplexes, thus establishing the exocyclic nature of the lesion. At the lesion site, alpha-OH-PdG rotates to a syn conformation, pairing to its counter cytosine residue that is protonated at pH 5.9. Three-dimensional models produced by restrained molecular dynamics simulations show different hydrogen-bonding patterns between the lesion and its cytosine partner and identify further stabilization of alpha-OH-PdG in a syn conformation by intra-residue hydrogen bonds. We compare the alpha-OH-PdG.dC duplex structure with that of duplexes containing the analogous lesion propano-dG and discuss the implications of our findings for the mutagenic bypass of acrolein lesions.

PubMed: 19223332
DOI: 10.1093/nar/gkp076

Experimental method

SOLUTION NMR