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...

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Bibliographic Details
Published in:Journal of biomolecular structure & dynamics 2008-02, Vol.25 (4), p.387-394
Main Authors: Neault, J. F., Diamantoglou, S., Beauregard, M., Nafisi, Sh, Tajmir-Riahi, H. A.
Format: Article
Language:English
Subjects:
Animals
Binding constant
Binding mode
Cattle
CD spectroscopy
Circular Dichroism
Drug
FTIR
Pharmaceutical Preparations - chemistry
Pharmaceutical Preparations - metabolism
Pharmacology
Protein
Protein Binding
Protein Denaturation - drug effects
Protein Folding
Protein Structure, Secondary
Ribonuclease, Pancreatic - chemistry
Ribonuclease, Pancreatic - metabolism
RNase A
Secondary structure
Spectrophotometry, Ultraviolet
Spectroscopy, Fourier Transform Infrared
UV-Visible
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Summary: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) × 10 4 M −1 , K aspirin = 3.57 (±1.4) × 10 4 M −1 , K cis-pt = 5.66 (±1.9) × 10 3 M −1 , and K ascorbate = 3.50 (±1.5) × 10 3 M −1 . Major protein unfolding occurred with reduction of α-helix from 29% (free protein) to 20% and increase of β-sheet from 39% (free protein) to 45% in the aspirin-, ascorbate-, and cis-Pt-RNase complexes, while minor increase of α-helix was observed for AZT-RNase adduct.
ISSN:0739-1102
1538-0254
DOI:10.1080/07391102.2008.10507187