TY - JOUR
T1 - New Tricks for Old Proteins
T2 - Single Mutations in a Nonenzymatic Protein Give Rise to Various Enzymatic Activities
AU - Moroz, Yurii S.
AU - Dunston, Tiffany T.
AU - Makhlynets, Olga V.
AU - Moroz, Olesia V.
AU - Wu, Yibing
AU - Yoon, Jennifer H.
AU - Olsen, Alissa B.
AU - McLaughlin, Jaclyn M.
AU - Mack, Korrie L.
AU - Gosavi, Pallavi M.
AU - Van Nuland, Nico A.J.
AU - Korendovych, Ivan V.
N1 - Publisher Copyright:
© 2015 American Chemical Society.
PY - 2015/11/10
Y1 - 2015/11/10
N2 - Design of a new catalytic function in proteins, apart from its inherent practical value, is important for fundamental understanding of enzymatic activity. Using a computationally inexpensive, minimalistic approach that focuses on introducing a single highly reactive residue into proteins to achieve catalysis we converted a 74-residue-long C-terminal domain of calmodulin into an efficient esterase. The catalytic efficiency of the resulting stereoselective, allosterically regulated catalyst, nicknamed AlleyCatE, is higher than that of any previously reported de novo designed esterases. The simplicity of our design protocol should complement and expand the capabilities of current state-of-art approaches to protein design. These results show that even a small nonenzymatic protein can efficiently attain catalytic activities in various reactions (Kemp elimination, ester hydrolysis, retroaldol reaction) as a result of a single mutation. In other words, proteins can be just one mutation away from becoming entry points for subsequent evolution.
AB - Design of a new catalytic function in proteins, apart from its inherent practical value, is important for fundamental understanding of enzymatic activity. Using a computationally inexpensive, minimalistic approach that focuses on introducing a single highly reactive residue into proteins to achieve catalysis we converted a 74-residue-long C-terminal domain of calmodulin into an efficient esterase. The catalytic efficiency of the resulting stereoselective, allosterically regulated catalyst, nicknamed AlleyCatE, is higher than that of any previously reported de novo designed esterases. The simplicity of our design protocol should complement and expand the capabilities of current state-of-art approaches to protein design. These results show that even a small nonenzymatic protein can efficiently attain catalytic activities in various reactions (Kemp elimination, ester hydrolysis, retroaldol reaction) as a result of a single mutation. In other words, proteins can be just one mutation away from becoming entry points for subsequent evolution.
UR - http://www.scopus.com/inward/record.url?scp=84948701202&partnerID=8YFLogxK
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U2 - 10.1021/jacs.5b07812
DO - 10.1021/jacs.5b07812
M3 - Article
C2 - 26555770
AN - SCOPUS:84948701202
SN - 0002-7863
VL - 137
SP - 14905
EP - 14911
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 47
ER -