biostudies-literatureBorghesani VNational Institutes of HealthNIGMS NIH HHSNIH HHSe202304367https://www.ebi.ac.uk/biostudies/studies/S-EPMC11045307biostudies-literatureUnknown30(24)Carbonic Anhydrases (CAs) have been a target for de novo protein designers due to the simplicity of the active site and rapid rate of the reaction. The first reported mimic contained a Zn(II) bound to three histidine imidazole nitrogens and an exogenous water molecule, hence closely mimicking the native enzymes' first coordination sphere. Co(II) has served as an alternative metal to interrogate CAs due to its d⁷ electronic configuration for more detailed solution characterization. We present here the Co(II) substituted [Co(II)(H₂O/OH^-)]_N(TRIL2WL23H)₃ ⁿ⁺ that behaves similarly to native Co(II) substituted human-CAs. Like the Zn(II) analogue, the cobalt-derivative at slightly basic pH is incapable of hydrolyzing p-nitrophenylaChemistry (Weinheim an der Bergstrasse, Germany)Co(II) Substitution Enhances the Esterase Activity of a de Novo Designed Zn(II) Carbonic Anhydrase.PMC11045307R01 GM1410861R01GM141086Tolbert AEBorghesani VPenner-Hahn JEZastrow MLPecoraro VLDeb AfalseCo(II) Substitution Enhances the Esterase Activity of a de Novo Designed Zn(II) Carbonic Anhydrase.Carbonic Anhydrases (CAs) have been a target for de novo protein designers due to the simplicity of the active site and rapid rate of the reaction. The first reported mimic contained a Zn(II) bound to three histidine imidazole nitrogens and an exogenous water molecule, hence closely mimicking the native enzymes' first coordination sphere. Co(II) has served as an alternative metal to interrogate CAs due to its d⁷ electronic configuration for more detailed solution characterization. We present here the Co(II) substituted [Co(II)(H₂O/OH^-)]_N(TRIL2WL23H)₃ ⁿ⁺ that behaves similarly to native Co(II) substituted human-CAs. Like the Zn(II) analogue, the cobalt-derivative at slightly basic pH is incapable of hydrolyzing p-nitrophenyla2024-01-01T00:00:00Z2024 Apr2026-06-02T06:37:32.545Z2026-04-15T03:15:18.822ZS-EPMC110453073837716910.1002/chem.202304367