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

The genome of the pathogenic bacterium Vibrio cholerae encodes for three carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the alpha-, beta- and gamma-classes. Here we report and anion inhibition study of the beta-CA, VchCA beta with anions and other small molecules which inhibit metalloenzymes. The best VchCA beta anion inhibitors were sulfamide, sulfamate, phenylboronic acid and phenylarsonic acid, which showed K(I)s in the range of 54-86 mu M. Diethyldithiocarbonate was also an effective VchCA beta 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(I)s of 2.3-9.5 mM. Identification of selective inhibitors of VchCA beta (over the human CA isoforms) may lead to pharmacological tools useful for understanding the physiological role(s) of this under-investigated enzyme. (C) 2016 Elsevier Ltd. All rights reserved.