Left-handed intercalated DNA double helix: rendezvous of ethidium and actinomycin D in the Z-helical conformation space

Journal of Biomolecular Structure & Dynamics
G GuptaR H Sarma

Abstract

It is now very well recognized that the DNA double helix is conformationally pluralistic and that this flexibility is derived from internal motions due to backbone torsions. But what is less apparent is that such internal motions can occur in a correlated fashion and express themselves in a wide variety of structural motifs and phenomena. For example, flexibility inherent in the DNA molecule can lead to a family of Z-DNA, LZ1 and LZ2 being the two extremes and correlated internal motion can cause LZ1 in equilibrium LZ2 transition. More interestingly, such motions manifest themselves as breathing modes on the DNA lattice resulting in the sequence specific intercalation sites. Following a detailed stereochemical analyses we observed that the intercalation site for ethidium is located at the dCpdG sequence of the intercalated LZ1 helix (LZ1*) while that for actinomycin D is located at the dGpdC sequence of the intercalated LZ2 helix (LZ2*). From the stereochemistry of the drug binding we make experimentally testable predictions which are in fact supported by a few recent experimental studies. These studies also show that a left-handed intercalated B-DNA model is a viable intermediate in the Z to B transition which can hold the dru...Continue Reading

Citations

Oct 12, 2000·Proceedings of the National Academy of Sciences of the United States of America·X QuJ B Chaires
Mar 1, 1984·Journal of Biomolecular Structure & Dynamics·A PohorilleR D MacElroy
Aug 1, 1984·Journal of Biomolecular Structure & Dynamics·S S Narula, M M Dhingra
Jun 11, 1984·Nucleic Acids Research·R H ShaferD Wade
Dec 1, 1988·European Journal of Biochemistry·F J Van de Ven, C W Hilbers
Sep 7, 2019·Biochimica Et Biophysica Acta. Molecular Cell Research·Imee M A Del MundoGuliang Wang
Mar 1, 1989·Biophysical Chemistry·L LeoniM Savino

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