Unique complex between bacterial azurin and tumor-suppressor protein p53

• Published in: Biochemical and biophysical research communications Vol. 332; no. 4; pp. 965 - 968
• Main Authors: Apiyo, David, Wittung-Stafshede, Pernilla
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.07.2005
• Subjects: Azurin; Azurin - chemistry; Bacteria; Binding Sites; Biophysics - methods; Blue-copper protein; Calorimetry; Chromatography, Gel; Circular Dichroism; Humans; Isothermal titration calorimetry; Kinetics; Oxidation-Reduction; Protein Binding; Protein Folding; Protein Structure, Secondary; Protein Structure, Tertiary; Protein–protein interactions; Pseudomonas aeruginosa; Pseudomonas aeruginosa - metabolism; Temperature; Thermodynamics; Tryptophan - chemistry; Tumor Suppressor Protein p53 - chemistry; Tumor-suppressor protein p53; Azurin; Protein–protein interactions; Tumor-suppressor protein p53; Isothermal titration calorimetry; Blue-copper protein; Circular dichroism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2005.05.038

The tumor-suppressor protein p53 is a major player in regulation of cell growth, genomic stability, and cell death. Recent work suggests that Pseudomonas aeruginosa azurin, as the only bacterial protein known to date, can enter cancer cells and interact with p53 promoting cell death. For the first time, here we demonstrate and characterize this proposed complex using purified proteins in vitro. We find that azurin binds to p53 with nanomolar affinity in a four-to-one stoichiometry (pH 7.5, 25 °C). Upon azurin binding, secondary structure is induced and tryptophan fluorescence is quenched, implying that interactions occur in the N-terminal p53 domain which is also the binding site for many oncogenes. Further biophysical studies may assist the design of novel cancer treatments that are based on azurin.