Activation studies of the α- and β-carbonic anhydrases from the pathogenic bacterium Vibrio cholerae with amines and amino acids

The alpha- and beta-class carbonic anhydrases (CAs, EC 4.2.1.1) from the pathogenic bacterium Vibrio cholerae, VchCA alpha, and VchCA beta, were investigated for their activation with natural and non-natural amino acids and amines. The most effective VchCA alpha activators were L-tyrosine, histamine, serotonin, and 4-aminoethyl-morpholine, which had K(A)s in the range of 8.21-12.0 mu M. The most effective VchCA beta activators were D-tyrosine, dopamine, serotonin, 2-pyridyl-methylamine, 2-aminoethylpyridine, and 2-aminoethylpiperazine, which had K(A)s in the submicromolar - low micromolar range (0.18-1.37 mu M). The two bacterial enzymes had very different activation profiles with these compounds, between each other, and in comparison to the human isoforms hCA I and II. Some amines were selective activators of VchCA beta, including 2-pyridylmethylamine (K-A of 180nm for VchCA beta, and more than 20 mu M for VchCA alpha and hCA I/II). The activation of CAs from bacteria, such as VchCA alpha/beta has not been considered previously for possible biomedical applications. It would be of interest to study in more detail the extent that CA activators are implicated in the virulence and colonisation of the host by such pathogenic bacteria, which for Vibrio cholerae, is highly dependent on the bicarbonate concentration and pH in the surrounding tissue.