Mercury metallation of the copper protein azurin and structural insight into possible heavy metal reactivity

• The structure of Hg2 + modified azurin has been elucidated by X-ray methods.
• Hg2 + binding was further confirmed by NMR, MALDI, and UV–visible spectroscopic methods.
• Evidence for copper displacement from wild type protein is observed.
• Bioinformatic analysis was used to identify homologous human protein domains.

Mercury(II) metallation of Pseudomonas aeruginosa azurin has been characterized structurally and biochemically. The X-ray crystal structure at 1.5 Å of mercury(II) metallated azurin confirms the coordination of mercury at the copper binding active site and a second surface site. These findings are further validated by NMR, Matrix-assisted laser desorption/ionization spectrometry (MALDI), and UV–visible spectroscopic methods indicating copper displacement from the wild-type protein. Bioinformatic analysis has identified homologous human protein domains computationally, and compared them to the structure of azurin, providing a model for human mercury interactions. Study of the mercury–azurin adduct, in combination with other known examples of protein–heavy metal interactions, could provide further insight into the chemical mechanisms of toxicological interactions, leading toward a global understanding of the biological speciation of toxic heavy metals.

The mercury adduct of P. aeruginosa azurin has been characterized structurally. The X-ray crystal structure at 1.5 Å confirms the coordination of mercury at the copper binding active site and at a second surface site. Bioinformatic analysis has identified homologous human protein domains, providing a model for human mercury interactions.Figure optionsDownload as PowerPoint slide