The DNA sequence at echinomycin binding sites determines the structural changes induced by drug binding: NMR studies of echinomycin binding to (d(ACGTACGT)) sub 2 and (d(TCGATCGA)) sub 2

Journal Article · Mon Mar 04 23:00:00 EST 1991 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00223a027· OSTI ID:5623635

Gilbert, D E; Feigon, J ^[1]

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1. Univ. of California, Los Angeles (United States)

The complexes formed between the cyclic octadepsipeptide antibiotic echinomycin and the two DNA octamers (d(ACGTACGT)){sub 2} and (d(TCGATCGA)){sub 2} have been investigated by using one- and two-dimensional proton NMR spectroscopy techniques. The results obtained for the two complexes are compared to each other, to the crystal structures of related DNA-echinomycin complexes, and to enzymatic ad chemical footprinting results. In the saturated complexes, two echinomycin molecules bind to each octamer by bisintercalation of the quinoxaline moieties on either side of each CpG step. Binding of echinomycin to the octamer (d(ACGTACGT)){sub 2} is cooperative so that only the two-drug complex is observed at lower drug-DNA ratios, but binding to (d(TCGATCGA)){sub 2} is not cooperative. Thus, the structure and stability of the DNA in echinomycin-DNA complexes depends on the sequence at and adjacent to the binding site. While the authors conclude that no single structural change in the DNA can explain all of the footprinting results, unwinding of the DNA helix in the drug-DNA complexes appears to be an important factor while Hoogsteen base pair formation does not.

• OSTI ID: 5623635
• Journal Information: Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 30:9; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
CHEMICAL SHIFT
CONFORMATIONAL CHANGES
DNA SEQUENCING
DNA-ASE
DRUGS
ENZYMES
ESTERASES
HYDROLASES
MAGNETIC RESONANCE
NMR SPECTRA
NUCLEAR MAGNETIC RESONANCE
NUCLEIC ACIDS
OLIGONUCLEOTIDES
ORGANIC COMPOUNDS
OVERHAUSER EFFECT
PHOSPHODIESTERASES
PROTEINS
RESONANCE
SPECTRA
STRUCTURAL CHEMICAL ANALYSIS