1. Evolution of a highly active and enantiospecific metalloenzyme from short peptides
- Author
-
Brian Kuhlman, Douglas A. Hansen, Bryan S. Der, Zbigniew Pianowski, Sabine Studer, Donald Hilvert, Aaron Debon, Peer R. E. Mittl, Sharon L. Guffy, University of Zurich, and Hilvert, Donald
- Subjects
Stereochemistry ,610 Medicine & health ,Peptide ,010402 general chemistry ,Cleavage (embryo) ,01 natural sciences ,Evolution, Molecular ,Metalloproteins ,10019 Department of Biochemistry ,Enzyme kinetics ,Catalytic efficiency ,Simultaneous optimization ,chemistry.chemical_classification ,1000 Multidisciplinary ,Multidisciplinary ,010405 organic chemistry ,Hydrolysis ,Esters ,Enzymes ,0104 chemical sciences ,Structure and function ,Zinc ,Enzyme ,chemistry ,Biocatalysis ,570 Life sciences ,biology ,Directed Molecular Evolution ,Oligopeptides - Abstract
Evolution trains a from-scratch catalyst Metal-bound peptides can catalyze simple reactions such as ester hydrolysis and may have been the starting point for the evolution of modern enzymes. Studer et al. selected progressively more-proficient variants of a small protein derived from a computationally designed zinc-binding peptide. The resulting enzyme could perform the trained reaction at rates typical for naturally evolved enzymes and serendipitously developed a strong preference for a single enantiomer of the substrate. A structure of the final catalyst highlights how small, progressive changes can remodel both catalytic residues and protein architecture in unpredictable ways. Science , this issue p. 1285
- Published
- 2018