1b60 | pdb_00001b60
3,N4-ETHENO-2'-DEOXYCYTIDINE OPPOSITE CYTIDINE IN AN 11-MER DUPLEX, SOLUTION STRUCTURE FROM NMR AND MOLECULAR DYNAMICS
|
Overview
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.
About this Structure
1B60 is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
Reference
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., Cullinan D, Johnson F, de los Santos C, J Mol Biol. 2000 Feb 25;296(3):851-61. PMID:10677286
Page seeded by OCA on Sat Nov 24 23:46:18 2007
