1B60

3,N4-ETHENO-2'-DEOXYCYTIDINE OPPOSITE CYTIDINE IN AN 11-MER DUPLEX, SOLUTION STRUCTURE FROM NMR AND MOLECULAR DYNAMICS

Summary for 1B60

• Entry DOI: 10.2210/pdb1b60/pdb
• Descriptor: DNA (5'-D(*CP*GP*TP*AP*CP*(EDC)P*CP*AP*TP*GP*C)-3'), DNA (5'-D(*GP*CP*AP*TP*GP*CP*GP*TP*AP*CP*G)-3') (2 entities in total)
• Functional Keywords: ethenodc, edc, exocyclic lesion, dna
• Total number of polymer chains: 2
• Total formula weight: 6692.39

Authors

Cullinan, D.,Johnson, F.,De Los Santos, C. (deposition date: 1999-01-20, release date: 2000-02-18, Last modification date: 2023-12-27)

Primary citation

Cullinan, D.,Johnson, F.,de los Santos, C.
Solution structure of an 11-mer duplex containing the 3, N(4)-ethenocytosine adduct opposite 2'-deoxycytidine: implications for the recognition of exocyclic lesions by DNA glycosylases.
J.Mol.Biol., 296:851-861, 2000

PubMed Abstract: Lipid peroxidation products, as well as the metabolic products of vinyl chloride, react with cellular DNA producing the mutagenic adduct 3,N(4)-etheno-2'-deoxycytidine (epsilondC), along with several other exocyclic derivatives. High-resolution NMR spectroscopy and restrained molecular dynamics simulations were used to establish the solution structure of an 11-mer duplex containing an epsilondC.dC base-pair at its center. The NMR data suggested a regular right-handed helical structure having all residues in the anti orientation around the glycosydic torsion angle and Watson-Crick alignments for all canonical base-pairs of the duplex. Restrained molecular dynamics generated a three-dimensional model in excellent agreement with the spectroscopic data. The (epsilondC. dC)-duplex structure is a regular right-handed helix with a slight bend at the lesion site and no severe distortions of the sugar-phosphate backbone. The epsilondC adduct and its partner dC were displaced towards opposite grooves of the helix, resulting in a lesion-containing base-pair that was highly sheared but stabilized to some degree by the formation of a single hydrogen bond. Such a sheared base-pair alignment at the lesion site was previously observed for epsilondC.dG and epsilondC.T duplexes, and was also present in the crystal structures of duplexes containing dG.T and dG. U mismatches. These observations suggest the existence of a substrate structural motif that may be recognized by specific DNA glycosylases during the process of base excision repair.

PubMed: 10677286
DOI: 10.1006/jmbi.1999.3490

Experimental method

SOLUTION NMR