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Updated: Jul 5, 2026

Iterative Optimization of DNA Duplexes for Crystallization of SeqA-DNA Complexes
Published on: November 1, 2012
Crystal structure of trioxacarcin A covalently bound to DNA
Roland Pfoh1, Hartmut Laatsch, George M Sheldrick
1Lehrstuhl für Strukturchemie, Georg-August-Universität, Tammannstr. 4, 37077 Göttingen, Germany.
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.
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