Distamycin A affects the stability of NF-kappaB p50-DNA complexes in a sequence-dependent manner

Speight, Robert E., Hart, Darren J., & Blackburn, Jonathan M. (2002) Distamycin A affects the stability of NF-kappaB p50-DNA complexes in a sequence-dependent manner. Journal of Molecular Recognition, 15(1), pp. 19-26.

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Abstract

The effect of two different DNA minor groove binding molecules, Hoechst 33258 and distamycin A, on the binding kinetics of NF-κB p50 to three different specific DNA sequences was studied at various salt concentrations. Distamycin A was shown to significantly increase the dissociation rate constant of p50 from the sequences PRDII (5′-GGGAAATTCC-3′) and Ig-κ B (5′-GGGACTTTCC-3′) but had a negligible effect on the dissociation from the palindromic target-κB binding site (5′-GGGAATTCCC-3′). By comparison, the effect of Hoechst 33258 on binding of p50 to each sequence was found to be minimal. The dissociation rates for the protein–DNA complexes increased at higher potassium chloride concentrations for the PRDII and Ig-κB binding motifs and this effect was magnified by distamycin A. In contrast, p50 bound to the palindromic target-κB site with a much higher intrinsic affinity and exhibited a significantly reduced salt dependence of binding over the ionic strength range studied, retaining a KD of less than 10 pM at 150 mM KCl. Our results demonstrate that the DNA binding kinetics of p50 and their salt dependence is strongly sequence-dependent and, in addition, that the binding of p50 to DNA can be influenced by the addition of minor groove-binding drugs in a sequence-dependent manner.

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5 citations in Web of Science®

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ID Code: 70984
Item Type: Journal Article
Refereed: Yes
Additional URLs:
Keywords: NF-KB, p50, distamycin A, Hoechst 33258, kinetic analysis, sequence-dependent drug effects, DNA conformation
DOI: 10.1002/jmr.556
ISSN: 1099-1352
Divisions: Current > Schools > School of Chemistry, Physics & Mechanical Engineering
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Deposited On: 04 May 2014 22:42
Last Modified: 25 Jun 2014 06:55

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