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

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• 作者：Alessio Innocenti ; Worraanong Leewattanapasuk ; Fritz A. Mü ; hlschlegel ; Antonio Mastrolorenzo ; Claudiu T. Supuran
• 关键词：Carbonic anhydrase ; Candida glabrata ; Candida albicans ; Anion ; Zinc-binding group ; Bicarbonate ; Antifungals
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2009
• 出版时间：15 August 2009
• 年：2009
• 卷：19
• 期：16
• 页码：4802-4805
• 全文大小：438 K

文摘

A β-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 × 10⁵ s⁻¹ and k_cat/K_M of 4.8 × 10⁷ M⁻¹ s⁻¹. The Cà glabrata CA (CgCA) was moderately inhibited by metal poisons (cyanide, azide, cyanate, thiocyanate, K_Is of 0.60–1.12 mM) but strongly inhibited by bicarbonate, nitrate, nitrite and phenylarsonic acid (K_Is of 86–98 μM). The other anions investigated showed inhibition constants in the low millimolar range, with the exception of bromide and iodide (K_Is of 27–42 mM).