2neo

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2neo

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SOLUTION NMR STRUCTURE OF A TWO-BASE DNA BULGE COMPLEXED WITH AN ENEDIYNE CLEAVING ANALOG, 11 STRUCTURES

Overview

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.

About this Structure

2NEO is a Protein complex structure of sequences from [1] with NCS as ligand. This structure superseeds the now removed PDB entry 1NEO. Full crystallographic information is available from OCA.

Reference

Solution structure of a two-base DNA bulge complexed with an enediyne cleaving analog., Stassinopoulos A, Ji J, Gao X, Goldberg IH, Science. 1996 Jun 28;272(5270):1943-6. PMID:8658168

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