Carbonic anhydrase inhibitors. Inhibition of the β-class enzyme from the pathogenic yeast Candida glabrata with anions

A beta-carbonic anhydrase (CA, EC 4.2.1.1), the protein encoded by the NCE103 gene of Candida glabrata which also present in Candida albicans and Saccharomyces cerevisiae, was cloned, purified, characterized kinetically and investigated for its inhibition by a series simple, inorganic anions such as halogenides, pseudohalogenides, bicarbonate, carbonate, nitrate, nitrite, hydrogen sulfide, bisulfite, perchlorate, sulfate and some isosteric species. The enzyme showed significant CO2 hydrase activity, with a k(cat) of 3.8 x 10(5) s(-1) and k(cat)/K-M of 4.8 x 10(7) M-1 s(-1). The Ca glabrata CA (CgCA) was moderately inhibited by metal poisons (cyanide, azide, cyanate, thiocyanate, K(I)s of 0.60-1.12 mM) but strongly inhibited by bicarbonate, nitrate, nitrite and phenylarsonic acid (K(I)s of 86-98 mu M). The other anions investigated showed inhibition constants in the low millimolar range, with the exception of bromide and iodide (KIs of 2742 mM). (C) 2009 Elsevier Ltd. All rights reserved.