Isomorphic deactivation of a Pseudomonas aeruginosa oxidoreductase: The crystal structure of Ag(I) metallated azurin at 1.7 Å

• The crystal structure of Pseudomonas aeruginosa azurin bound to Ag(I) is presented.
• Azurin’s ligation geometry to Ag(I) is isomorphic to Cu(I/II).
• NMR, mass spectrometry and cyclic voltammetry support the structure.
• Visible spectra showed that Ag(I) can replace Cu(II) rapidly.
• These results show that Ag(I)-based antimicrobials may replace copper in proteins.

Multiple biophysical methods demonstrate that silver effectively metallates Pseudomonas aeruginosa apo-azurin in solution. X-ray crystallography of the silver-modified protein reveals that silver binds to azurin at the traditional copper mediated active site with nearly identical geometry. Cyclic voltammetry indicates that the silver adduct is redox inert. Our results suggest that a potential mechanism for the microbial toxicity of silver is the deactivation of copper oxidoreductases by the effective binding and structural mimicry by silver without the corresponding function.

Multiple biophysical methods demonstrate that Ag(I) ion effectively metallates P. aeruginosa apo-azurin in solution. NMR spectroscopy and X-ray crystallography of the protein adduct reveal that silver binds to azurin at the traditional copper mediated active site with a nearly identical geometry. Cyclic voltammetry indicates that the silver adduct is redox inert.Figure optionsDownload as PowerPoint slide