SOLUTION STRUCTURE OF A 2-BASE DNA BULGE COMPLEXED WITH AN ENEDIYNE CLEAVING ANALOG

Citation
A. Stassinopoulos et al., SOLUTION STRUCTURE OF A 2-BASE DNA BULGE COMPLEXED WITH AN ENEDIYNE CLEAVING ANALOG, Science, 272(5270), 1996, pp. 1943-1946
Citations number
44
Categorie Soggetti
Multidisciplinary Sciences
Journal title
ISSN journal
00368075
Volume
272
Issue
5270
Year of publication
1996
Pages
1943 - 1946
Database
ISI
SICI code
0036-8075(1996)272:5270<1943:SSOA2D>2.0.ZU;2-V
Abstract
Nucleic acid bulges have been implicated in a number of biological pro cesses and are specific cleavage targets for the enediyne antitumor an tibiotic neocarzinostatin chromophore in a base-catalyzed, radical-med iated reaction. The solution structure of the complex between an analo g of the bulge-specific cleaving species and an oligodeoxynucleotide c ontaining a two-base bulge was elucidated by nuclear magnetic resonanc e. An unusual binding mode involves major groove recognition by the dr ug 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 bulg e nucleotide. This structure clarifies the mechanism of bulge recognit ion and cleavage by a drug and provides insight into the design of bul ge-specific nucleic acid binding molecules.