Anion inhibition studies of the β-carbonic anhydrase from the pathogenic bacterium Vibrio cholerae

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• 作者：Daniela Vullo^a ; Sonia Del Prete^a ; ^b ; Viviana De Luca^b ; Vincenzo Carginale^b ; Marta Ferraroni^a ; Nurcan Dedeoglu^a ; Sameh M. Osman^c ; Zeid AlOthman^c ; Clemente Capasso^b ; ^{clemente.capasso@ibbr.cnr.it" class="auth_mail" title="E-mail the corresponding author} ; Claudiu T. Supuran^c ; ^d ; ^{claudiu.supuran@unifi.it" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Carbonic anhydrase ; Metalloenzymes ; Inhibitors ; Anions ; Pathogenic bacteria ; Hydratase activity ; Vibrio cholerae
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 March 2016
• 年：2016
• 卷：26
• 期：5
• 页码：1406-1410
• 全文大小：834 K

文摘

The genome of the pathogenic bacterium Vibrio cholerae encodes for three carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the α-, β- and γ-classes. Here we report and anion inhibition study of the β-CA, VchCAβ with anions and other small molecules which inhibit metalloenzymes. The best VchCAβ anion inhibitors were sulfamide, sulfamate, phenylboronic acid and phenylarsonic acid, which showed K_Is in the range of 54–86 μM. Diethyldithiocarbonate was also an effective VchCAβ inhibitor, with an inhibition constant of 0.73 mM. The halides, cyanate, thiocyanate, cyanide, bicarbonate, carbonate, nitrate, nitrite, stannate, selenate, tellurate, divanadate, tetraborate, perrhenate, perruthenate, peroxydisulfate, selenocyanide, trithiocarbonate, and fluorosulfonate showed affinity in the low millimolar range, with K_Is of 2.3–9.5 mM. Identification of selective inhibitors of VchCAβ (over the human CA isoforms) may lead to pharmacological tools useful for understanding the physiological role(s) of this under-investigated enzyme.