A DeNovo Designed Metalloenzyme for the Hydration of CO sub(2)

• Published in: Angewandte Chemie International Edition Vol. 53; no. 30; pp. 7900 - 7903
• Main Authors: Cangelosi, Virginia M, Deb, Aniruddha, Penner-Hahn, James E, Pecoraro, Vincent L
• Format: Journal Article
• Language: English
• Published: 01-07-2014
• Subjects: Affinity; Bundling; Carbon dioxide; Carbonic anhydrase; Enzymes; Hydration; Proteins; Stability; Zinc
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201404925

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 super(II) metalloenzyme was prepared using denovo design. [alpha] sub(3)DH sub(3) folds into a stable single-stranded three-helix bundle and binds Zn super(II) with high affinity using His sub(3)O coordination. The resulting metalloenzyme catalyzes the hydration of CO sub(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 anhydraseII, one of the most efficient enzymes known. This designed zinc enzyme performs better than small-molecule models of carbonic anhydrase. Picture: Znpurple, Ndark blue, Ored, Ccyan.