title: Crystallographic characterization of an exocyclic DNA adduct: 3,N4-etheno-2'-deoxycytidine in the dodecamer 5'-CGCGAATTepsilonCGCG-3'.
abstract: Exocyclic DNA adducts are formed from metabolites of chemical carcinogens and have also been detected as endogenous lesions in human DNA. The exocyclic adduct 3,N(4)-etheno-2'-deoxycytidine (epsilon dC), positioned opposite deoxyguanosine in the B-form duplex of the dodecanucleotide d(CGCGAATTepsilonCGCG), has been crystallographically characterized at 1.8A resolution. This self-complementary oligomer crystallizes in space group P3(2)12, containing a single strand in the asymmetric unit. The crystal structure was solved by isomorphous replacement with the corresponding unmodified dodecamer structure. Exposure of both structures to identical crystal packing forces allows a detailed investigation of the influence of the exocyclic base adduct on the overall helical structure and local geometry. Structural changes are limited to the epsilon C:G and adjacent T:A and G:C base-pairs. The standard Watson-Crick base-pairing scheme, retained in the T:A and G:C base-pairs, is blocked by the etheno bridge in the epsilon C:G pair. In its place, a hydrogen bond involving O2 of epsilon C and N1 of G is present. Comparison with an epsilon dC-containing NMR structure confirms the general conformation reported for epsilon C:G, including the hydrogen bonding features. Superposition with the crystal structure of a DNA duplex containing a T:G wobble pair shows similar structural changes imposed by both mismatches. Evaluation of the hydration shell of the duplex with bond valence calculations reveals two sodium ions in the crystal.
authors.affiliation: Department of Pharmacological Sciences, Center for Structural Biology, State University of New York at Stony Brook, Stony Brook, NY 11794-5115, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Freisinger
authors.forename: Andrea
authors.initials: A
authors.lastname: Fernandes
authors.forename: Arthur P
authors.initials: AP
authors.lastname: Grollman
authors.forename: Caroline
authors.initials: C
authors.lastname: Kisker
mesh_terms: D001482:Base Composition; D020029:Base Pairing; D018360:Crystallography, X-Ray; D018736:DNA Adducts / Q000737:chemistry*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000737:chemistry*; D006151:Guanosine / Q000737:chemistry; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D013816:Thermodynamics; D013936:Thymidine / Q000737:chemistry
chemical_list: D018736:DNA Adducts; D009838:Oligodeoxyribonucleotides; D003841:Deoxycytidine; D006151:Guanosine; C032222:3,N(4)-ethenodeoxycytidine; D013936:Thymidine