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

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