Conformational analysis of Na,K-ATPase in drug–protein complexes

This review reports the effects of several drugs such as AZT (anti-AIDS), cis-Pt (antitumor), aspirin (anti-inflammatory) and vitamin C (antioxidant) on the stability and conformation of Na,K-ATPase in vitro. Drug–enzyme binding was found to be via H-bonding to the polypeptide CO and C–N groups with two binding constants K1(AZT) = 5.30 (±2.1) × 105 M−1 and K2(AZT) = 9.80 (±2.9) × 103 M−1 for AZT and one binding constant Kcis-Pt = 1.93 (±1.2) × 104 M−1 for cis-Pt, Kaspirin = 6.45 (±2.5) × 103 M−1 and Kascorbate = 1.04 (±0.5) × 104 M−1 for aspirin and ascorbic acid. The enzyme secondary structure was altered with major increase of α-helix from 19.9% (free protein) to 22–26% and reduction of β-sheet from 25.6% (free protein) to 17–23% upon drug complexation indicating a partial stabilization of protein conformation. The order of induced stability is AZT>cis-Pt > ascorbate > aspirin.