AZT Binding to Na,K-ATPase

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In this Subject: Biology
By this author: A. Ahmed-Ouameur ;&nbsp; J.-F. Neault ;&nbsp; S. Claveau ;&nbsp; H. A. Tajmir-Riahi

Authors: A. Ahmed-Ouameur; J.-F. Neault; S. Claveau; H. A. Tajmir-Riahi

Source: Cell Biochemistry and Biophysics, Volume 42, Number 1, February 2005 , pp. 87-94(8)

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Abstract:

3'-azido-3'-deoxythymidine (AZT) is the first effective drug used clinically for the treatment of human immunodeficiency virus (HIV) infection. The drug interactions with DNA and protein are associated with its mechanism of action in vivo. This study was designed to examine the interaction of AZT with the Na,K-dependent adenosine triphosphatase (Na,K-ATPase) in H2O and D2O solutions at physiological pH using drug concentration of 0.1 µM to 1 mM and final protein concentration of 0.5 to 1 mg/mL. Ultraviolet absorption and Fourier transform infrared difference spectroscopy with its self-deconvolution, second-derivative resolution enhancement, and curve-fitting procedures were used to characterize the drug-binding mode, the drug-binding constant, and the effects of drug interaction on the protein secondary structure. Spectroscopic evidence showed that at low drug concentration (0.1 µM), AZT binds (H-bonding) mainly to the polypeptide C=O and C-N groups with two binding constants of K1 = 5.3 × 105 M<I+>–1 and K2 = 9.8 × 103 M<I+>–1. As drug content increased, AZT-lipid complex prevailed. At a high drug concentration (1 mM), drug binding resulted in minor protein secondary structural changes from that of the alpha