Hydrophobic Substituents of the Phenylmethylsulfamide Moiety Can Be Used for the Development of New Selective Carbonic Anhydrase Inhibitors

Figure 3

(a) Active site region of the hCA II/14 complex. The inhibitor is shown in association with a σA-weighted || map (at 1.0 σ). Hydrogen bonds, van der Waals interactions (distance of <4.0 Å), and the active site Zn²⁺-ion coordination are also shown. (b, c, d, and e) Solvent accessible surface of hCAs II, IX, XII, and I: the hydrophobic cleft defined by residues 131, 135, 202, and 204 is highlighted in orange (hCA II), blue (hCA IX), green (hCA XII), and magenta (hCA I). For hCA I His200 is also showed in magenta. (f) Structural superposition of the hCA I (magenta) and hCA II (green) active sites. The inhibitor 14 is shown as bound in its complex with hCA II.

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