title: Conformational analysis of Na,K-ATPase in drug-protein complexes.
abstract: 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 K(1(AZT))=5.30 (+/-2.1)x10(5)M(-1) and K(2(AZT))=9.80 (+/-2.9)x10(3)M(-1) for AZT and one binding constant K(cis)(-Pt)=1.93 (+/-1.2)x10(4)M(-1) for cis-Pt, K(aspirin)=6.45 (+/-2.5)x10(3)M(-1) and K(ascorbate)=1.04 (+/-0.5)x10(4)M(-1) for aspirin and ascorbic acid. The enzyme secondary structure was altered with major increase of alpha-helix from 19.9% (free protein) to 22-26% and reduction of beta-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.
authors: Department of Chemistry-Biology, University of Québec at Trois-Rivières, C.P. 500, Trois-Rivieres, Québec, Canada G9A 5H7.
authors: J F
authors: JF
authors: Neault
authors: S
authors: S
authors: Diamantoglou
authors: Sh
authors: Sh
authors: Nafisi
authors: H A
authors: HA
authors: Tajmir-Riahi
mesh_terms: D000818:Animals; D004795:Enzyme Stability / Q000187:drug effects; D006168:Guinea Pigs; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry* / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D014867:Water / Q000737:chemistry
chemical_list: D004364:Pharmaceutical Preparations; D014867:Water; D000254:Sodium-Potassium-Exchanging ATPase