Effects of nucleoside analog incorporation on DNA binding to the DNA binding domain of the GATA‐1 erythroid transcription factor

FEBS Letters

Stahl, Stephen²  Schweitzer, Barry I¹  West, John¹  Maloney, Donna¹  Foti, Matthew¹  Omichinski, James G² 

[1] Walt Disney Memorial Cancer Institute at Florida Hospital, 12722 Research Parkway, Orlando, FL 32826, USA;Laboratory of Chemical Physics, NIDDK, National Institutes of Health, Bethesda, MD 20892-0520, USA

关键词: Ganciclovir;    Cytosine arabinoside;    GATA-1;    Binding;    Nuclear magnetic resonance;   

DOI  :  10.1016/S0014-5793(99)00026-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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. ¹H-¹⁵N 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.

【 授权许可】

Unknown