A De Novo Designed Metalloenzyme for the Hydration of CO 2

Abstract

Protein design will ultimately allow for the creation of artificial enzymes with novel functions and unprecedented stability. To test our current mastery of nature’s approach to catalysis, a Zn II metalloenzyme was prepared using de novo design. α 3 DH 3 folds into a stable single‐stranded three‐helix bundle and binds Zn II with high affinity using His 3 O coordination. The resulting metalloenzyme catalyzes the hydration of CO 2 better than any small molecule model of carbonic anhydrase and with an efficiency within 1400‐fold of the fastest carbonic anhydrase isoform, CAII, and 11‐fold of CAIII. Chasing down the cheetah : A synthetic metalloenzyme was created that is capable of catalyzing the hydration of carbon dioxide with an efficiency within 1400‐fold of carbonic anhydrase II, one of the most efficient enzymes known. This designed zinc enzyme performs better than small‐molecule models of carbonic anhydrase. Picture: Zn purple, N dark blue, O red, C cyan.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108029/1/anie_201404925_sm_miscellaneous_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/108029/2/7900_ftp.pd