Carbonic anhydrase inhibitors. Inhibition of the β-class enzyme from the yeast Saccharomyces cerevisiae with anions

• Published in: Bioorganic & medicinal chemistry 2008-12, Vol.18 (24), p.6327-6331
• Main Authors: Isik, Semra, Kockar, Feray, Arslan, Oktay, Guler, Ozen Ozensoy, Innocenti, Alessio, Supuran, Claudiu T.
• Format: Article
• Language: English
• Subjects: Acetazolamide - chemistry; Amino Acid Sequence; Analytical, structural and metabolic biochemistry; Anions; Biological and medical sciences; Bromides - chemistry; Candida albicans; Candida albicans - metabolism; Carbonic anhydrase; Carbonic Anhydrase Inhibitors - chemical synthesis; Carbonic Anhydrase Inhibitors - pharmacology; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - pharmacology; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Inorganic anion; Iodide; Iodides - chemistry; Isoenzymes - chemistry; Kinetics; Lyases; Models, Chemical; Molecular Sequence Data; Nce103 gene; Saccharomyces cerevisiae; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - metabolism; Sequence Homology, Amino Acid; Sulfamide; Sulfides - chemistry; Yeast
• ISSN: 0960-894X; 0968-0896; 1464-3405; 1464-3391
• DOI: 10.1016/j.bmcl.2008.10.100

The protein encoded by the Nce103 gene of Saccharomyces cerevisiae, a β-carbonic anhydrase (CA, EC 4.2.1.1) designated as scCA, has been cloned, purified, characterized kinetically, and investigated for its inhibition with a series simple, inorganic anions such as halogenides, pseudohalogenides, bicarbonate, carbonate, nitrate, nitrite, hydrogen sulfide, bisulfite, perchlorate, sulfate, and some of its isosteric species. The enzyme showed high CO 2 hydrase activity, with a k cat of 9.4 × 10 5 s −1 and k cat/ K m of 9.8 × 10 7 M −1 s −1. scCA was weakly inhibited by metal poisons (cyanide, azide, cyanate, thiocyanate, K Is of 16.8–55.6 mM) and strongly inhibited by bromide, iodide, and sulfamide ( K Is of 8.7–10.8 μM). The other investigated anions showed inhibition constants in the low millimolar range.