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,
\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.