Protein unfolding in drug-RNase complexes.
Bovine pancreatic ribonuclease A (RNase A) catalyzes the cleavage of P-O5' bonds in RNA on the 3' side of pyrimidine to form cyclic 2', 5'-phosphates. It has several high affinity binding sites that make it possible target for many organic and inorganic molecules. Ligand binding to RNase A can alter protein secondary structure and its catalytic activity. In this review, 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 RNase A in vitro are compared. The results of UV-visible, FTIR, and CD spectroscopic analysis of RNase complexes with aspirin, AZT, cis-Pt, and vitamin C at physiological conditions are discussed here. Spectroscopic results showed one major binding for each drug-RNase adduct with KAZT=5.29 (+/-1.6)x10(4) M(-1), Kaspirin=3.57 (+/-1.4)x10(4) M(-1), Kcis-Pt=5.66 (+/-1.9)x10(3) M(-1), and Kascorbate=3.50 (+/-1.5)x10(3) M(-1). Major protein unfolding occurred with reduction of alpha-helix from 29% (free protein) to 20% and increase of beta-sheet from 39% (free protein) to 45% in the aspirin-, ascorbate-, and cis-Pt-RNase complexes, while minor increase of alpha-helix was observed for AZT-RNase adduct.
Neault
J F
JF
Department of Chemistry-Biology, University of Québec at Trois-Rivières, Canada G9A 5H7.
Diamantoglou
S
S
Beauregard
M
M
Nafisi
Sh
Sh
Tajmir-Riahi
H A
HA
D000818:Animals; D002417:Cattle; D002942:Circular Dichroism; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism*; D010600:Pharmacology; D011485:Protein Binding; D011489:Protein Denaturation / Q000187:drug effects; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012259:Ribonuclease, Pancreatic / Q000737:chemistry* / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared
D004364:Pharmaceutical Preparations; D012259:Ribonuclease, Pancreatic