Designer Protein Loves Metal

Scientists envision that someday computationally designed proteins could bind metals and catalyze chemical reactions unseen in nature for industrial and medical applications. A team has taken a step in that direction by generating a novel metal-binding protein that incorporates an unnatural amino acid with an exquisite taste for metals (J. Am. Chem. Soc. 2013, DOI: 10.1021/ja403503m). The researchers, led by David Baker of the University of Washington, Seattle, used an unnatural amino acid because no single amino acid typically found in proteins can bind metals unaided. They used (2,2ʹ-bipyridin-5-yl)alanine, or Bpy-Ala, which alone has micromolar-level affinities for a variety of metals. The researchers instructed their computer program to place Bpy-Ala within a rigid part of a protein, such as an α-helix, to lock the unnatural amino acid in place. After expressing the computer-designed protein in bacteria, the team solved its crystal structure and found that it matches the design almost exactly. The team also found that the designed protein binds cobalt, zinc, iron, and nickel with affinities in the picomolar to micromolar range.