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The origins of sequence specificity of ethidium nucleic acid intercalation
Author(s) -
Pack George R.,
Loew Gilda H.
Publication year - 2009
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.560120710
Subject(s) - intercalation (chemistry) , nucleic acid , dna , chemistry , sequence (biology) , base pair , nucleic acid structure , crystallography , pyrimidine , stereochemistry , biochemistry , biophysics , rna , biology , organic chemistry , gene
The specificity of the intercalating dye ethidium for pyrimidine (3'‐5') purine sequences in nucleic acid is studied. The known crystal structure of a complex of Iodo UpA with intercalated ethidium is utilized as a model for the binding. The energetics of the conformation changes from DNA‐B to the intercalation geometry are examined for all possible dinucleotide pairs which could comprise the intercalation site. It is shown that differences in base‐backbone interactions lead to sequence‐dependent energetics of these conformational changes. Moreover, the calculated order of “unwinding” energies for different sites corresponds to the observed sequence isomer specificity for binding of ethidium to helical segments of nucleic acids. Thus the specificity appears to be largely a consequence of the different energetics of conformational changes within the nucleic acid sites. It is proposed that other intercalating molecules which require the same unwinding changes as ethidium will exhibit similar specificity.