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.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Pfoh R,Laatsch H,Sheldrick GMdoi
10.1093/nar/gkn245subject
Has Abstractpub_date
2008-06-01 00:00:00pages
3508-14issue
10eissn
0305-1048issn
1362-4962pii
gkn245journal_volume
36pub_type
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