title: Crystal structure of trioxacarcin A covalently bound to DNA.
abstract: We report a crystal structure that shows an antibiotic that extracts a nucleobase from a DNA molecule 'caught in the act' after forming a covalent bond but before departing with the base. The structure of trioxacarcin A covalently bound to double-stranded d(AACCGGTT) was determined to 1.78 A resolution by MAD phasing employing brominated oligonucleotides. The DNA-drug complex has a unique structure that combines alkylation (at the N7 position of a guanine), intercalation (on the 3'-side of the alkylated guanine), and base flip-out. An antibiotic-induced flipping-out of a single, nonterminal nucleobase from a DNA duplex was observed for the first time in a crystal structure.
authors.affiliation: Lehrstuhl für Strukturchemie, Georg-August-Universität, Tammannstr. 4, 37077 Göttingen, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Pfoh
authors.forename: Hartmut
authors.initials: H
authors.lastname: Laatsch
authors.forename: George M
authors.initials: GM
authors.lastname: Sheldrick
mesh_terms: D000617:Aminoglycosides / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; C033790:trioxacarcin; D004247:DNA