2NEO

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

Replaces:  1NEO

Summary for 2NEO

• Entry DOI: 10.2210/pdb2neo/pdb
• Descriptor: DNA (5'-D(*CP*CP*CP*GP*AP*TP*GP*CP*PGE*GP*CP*AP*AP*TP*TP*CP*GP*GP*G)-3'), SPIRO[[7-METHOXY-5-METHYL-1,2-DIHYDRO-NAPHTHALENE]-3,1'-[5-HYDROXY-9-[2-METHYLAMINO-2,6-DIDEOXYGALACTOPYRANOSYL-OXY]-5-(2-OXO-[1,3]DIOXOLAN-4-YL)-3A,5,9,9A-TETRAHYDRO-3H-1-OXA-CYCLOPENTA[A]-S-INDACEN-2-ONE]] (2 entities in total)
• Functional Keywords: dna, bulge dna, enediyne antibiotics antitumor agents, carbohydrates, bulge binding ligands, deoxyribonucleic acid
• Total number of polymer chains: 1
• Total formula weight: 6312.39

Authors

Stassinopoulos, A.,Ji, J.,Gao, X.,Goldberg, I.H. (deposition date: 1997-06-19, release date: 1998-01-28, Last modification date: 2024-05-22)

Primary citation

Stassinopoulos, A.,Ji, J.,Gao, X.,Goldberg, I.H.
Solution structure of a two-base DNA bulge complexed with an enediyne cleaving analog.
Science, 272:1943-1946, 1996

PubMed 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.

PubMed: 8658168

Experimental method

SOLUTION NMR