Solution structure of a two-base DNA bulge complexed with an enediyne cleaving analog.
Science
; 272(5270): 1943-6, 1996 Jun 28.
Article
en En
| MEDLINE
| ID: mdl-8658168
ABSTRACT
Nucleic acid bulges have been implicated in a number of biological processes and are specific cleavage targets for the enediyne antitumor antibiotic neocarzinostatin chromophore in a base-catalyzed, radical-mediated reaction. The solution structure of the complex between an analog of the bulge-specific cleaving species and an oligodeoxynucleotide containing a two-base bulge was elucidated by nuclear magnetic resonance. An unusual binding mode involves major groove recognition by the drug carbohydrate unit and tight fitting of the wedge-shaped drug in the triangular prism pocket formed by the two looped-out bulge bases and the neighboring base pairs. The two drug rings mimic helical DNA bases, complementing the bent DNA structure. The putative abstracting drug radical is 2.2 +/- 0.1 angstroms from the pro-S H5' of the target bulge nucleotide. This structure clarifies the mechanism of bulge recognition and cleavage by a drug and provides insight into the design of bulge-specific nucleic acid binding molecules.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Oligodesoxirribonucleótidos
/
ADN
/
Conformación de Ácido Nucleico
Idioma:
En
Revista:
Science
Año:
1996
Tipo del documento:
Article
País de afiliación:
Estados Unidos