Multiple Binding Modes of Inhibitors to Carbonic Anhydrases: How to Design Specific Drugs Targeting 15 Different Isoforms?

Abstract

Carbonic anhydrases (CAs, EC 4.2.1.1) are ubiquitous metalloenzymes, present throughout most living organisms and encoded by five evolutionarily unrelated gene families: the α-, β-, γ-, δ-, and ζ-CAs The α- β- and δ-CAs contain a Zn(II) ion at the active site, the γ-CAs are probably Fe(II) enzymes (but they are active also with Zn(II) or Co(II) ions), while the metal ion is usually replaced by cadmium in the ζ-CAs. Herein we report a state of the art structural crystallographyc investigation.