New Tricks for Old Proteins: Single Mutations in a Nonenzymatic Protein Give Rise to Various Enzymatic Activities

• DOI: 10.1021/jacs.5b07812
• Publication Date: 2015-11-10T16:15:04Z
• Authors: Yurii S. Moroz; Tiffany T. Dunston; Olga V. Makhlynets; Olesia V. Moroz; Yibing Wu; Jennifer H. Yoon; Alissa B. Olsen; Jaclyn M. McLaughlin; Korrie L. Mack; Pallavi M. Gosavi; Nico A. J. van Nu...; Ivan V. Korendovych
• Keywords: Protein design; Residue (chemistry); Protein Engineering; Catalytic efficiency

Design of a new catalytic function in proteins, apart from its inherent practical value, is important for fundamental understanding enzymatic activity. Using computationally inexpensive, minimalistic approach that focuses on introducing single highly reactive residue into proteins to achieve catalysis we converted 74-residue-long C-terminal domain calmodulin an efficient esterase. The efficiency the resulting stereoselective, allosterically regulated catalyst, nicknamed AlleyCatE, higher than any previously reported de novo designed esterases. simplicity our design protocol should complement and expand capabilities current state-of-art approaches protein design. These results show even small nonenzymatic can efficiently attain activities various reactions (Kemp elimination, ester hydrolysis, retroaldol reaction) as result mutation. In other words, be just one mutation away becoming entry points subsequent evolution.