Carbonic anhydrase inhibitors. Inhibition of the beta-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 Saccharomycescerevisiae, 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 CO(2) 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 Cà 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 microM). The other anions investigated showed inhibition constants in the low millimolar range, with the exception of bromide and iodide (K(I)s of 27-42 mM).
Innocenti
Alessio
A
Laboratorio di Chimica Bioinorganica, Università degli Studi di Firenze, I-50019 Sesto Fiorentino, Firenze, Italy.
Leewattanapasuk
Worraanong
W
Mühlschlegel
Fritz A
FA
Mastrolorenzo
Antonio
A
Supuran
Claudiu T
CT
D000595:Amino Acid Sequence; D000838:Anions / Q000494:pharmacology*; D041221:Candida glabrata / Q000201:enzymology*; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D000838:Anions; D002257:Carbonic Anhydrase Inhibitors; D020033:Protein Isoforms; D002256:Carbonic Anhydrases