Three Protein Copper Sites Interconnected

The copper sites in cupredoxins, a family of proteins that facilitate a variety of redox activities, are structurally and functionally diverse. As little as 10% of their amino acid sequence is identical. Nevertheless, the copper sites are always found within a similar β-barrel protein structure and may be evolutionarily linked. Studies on the binuclear Cu_A (purple) site of nitrous oxide reductase (N₂OR) by Masha G. Savelieff, Yi Lu, and coworkers at the University of Illinois, Urbana-Champaign, now provide experimental evidence for that connection (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.0711316105). The researchers added copper to metal-free protein and observed by electronic absorption and electron paramagnetic resonance spectroscopy that copper was first incorporated almost equally in separate type 1 (blue) and type 2 (red) sites. Over time the separate sites converted to the binuclear Cu_A structure. “These observations suggest that the purple Cu_A site contains the essential elements of type 1 and type 2 copper centers” and provide insight into the evolutionary relationships among cupredoxin proteins, the authors write.