title: A de novo designed metalloenzyme for the hydration of CO2.
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. α3DH3 folds into a stable single-stranded three-helix bundle and binds Zn(II) with high affinity using His3 O coordination. The resulting metalloenzyme catalyzes the hydration of CO2 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.
authors.affiliation: Department of Chemistry, University of Michigan, Ann Arbor MI, 48109 (USA).
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Cangelosi
authors.forename: Aniruddha
authors.initials: A
authors.lastname: Deb
authors.forename: James E
authors.initials: JE
authors.lastname: Penner-Hahn
authors.forename: Vincent L
authors.initials: VL
authors.lastname: Pecoraro
mesh_terms: D001665:Binding Sites; D002245:Carbon Dioxide / Q000737:chemistry*; D002256:Carbonic Anhydrases / Q000737:chemistry*; D002384:Catalysis; D008667:Metalloproteins / Q000737:chemistry*; D008958:Models, Molecular; D013329:Structure-Activity Relationship
chemical_list: D008667:Metalloproteins; D002245:Carbon Dioxide; D002256:Carbonic Anhydrases
keywords: carbonic anhydrase; de novo design; metalloenzymes; protein design; zinc enzymes