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Effects of nucleoside analog incorporation on DNA binding to the DNA binding domain of the GATA‐1 erythroid transcription factor
Author(s) -
Foti Matthew,
Omichinski James G,
Stahl Stephen,
Maloney Donna,
West John,
Schweitzer Barry I
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00026-5
Subject(s) - dna , chemistry , guanine , binding domain , hmg box , microbiology and biotechnology , dna binding site , dna binding domain , binding site , nucleoside , ganciclovir , biochemistry , transcription factor , dna binding protein , biology , nucleotide , gene , promoter , gene expression , human cytomegalovirus
We investigate here the effects of the incorporation of the nucleoside analogs araC (1‐β‐ d ‐arabinofuranosylcytosine) and ganciclovir (9‐[(1,3‐dihydroxy‐2‐propoxy)methyl] guanine) into the DNA binding recognition sequence for the GATA‐1 erythroid transcription factor. A 10‐fold decrease in binding affinity was observed for the ganciclovir‐substituted DNA complex in comparison to an unmodified DNA of the same sequence composition. AraC substitution did not result in any changes in binding affinity. 1 H‐ 15 N HSQC and NOESY NMR experiments revealed a number of chemical shift changes in both DNA and protein in the ganciclovir‐modified DNA‐protein complex when compared to the unmodified DNA‐protein complex. These changes in chemical shift and binding affinity suggest a change in the binding mode of the complex when ganciclovir is incorporated into the GATA DNA binding site.