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Figure 3.
Fig. 3. Active site and inhibition of Can2. (a) Active site
of Can2 with electron density contoured at 1.0 σ. Coordination
of the active-site Zn^2+ by Cys68, His124, Cys127, and a water
molecule is indicated by black broken lines, and the hydrogen
bond from the water molecule to Asp70 is colored orange. (b)
Overlay of the active sites of Can2 and the plant-type β-CAs of
E. coli (yellow) and P. sativum (dark red) and the Cab-type
β-CAs of M. thermoautotrophicum (green) and M. tuberculosis
Rv1284 (gray). The Zn^2+ ions are shown as orange spheres, and
the water molecules are colored according to the organism. (c)
Chemical structure of the most potent inhibitors identified for
Can2, AAZ, and benzolamide. (d) Detrimental effect of the Can2
inhibitors AAZ and benzolamide on the growth of the C. albicans
Nce103 deletion mutant expressing CAN2 (RH1). RH1 was spotted
onto YNB agar at 1 × 10^5, 1 × 10^4, and 1 ×
10^3 cells/ml in the presence of (i) 4% DMSO and 3 mM
benzolamide for 96 h or (ii) 4% DMSO and 3 mM AAZ for 72 h.
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