Cloning, Characterization, and Inhibition Studies of a β-Carbonic Anhydrase from Brucella suis

A beta-carbonic anhydrase (CA, EC 4.2.1.1) from the bacterial pathogen Brucella suis, bsCA 1, has been cloned, purified, and characterized kinetically. bsCA I has appreciable activity as catalyst for the hydration of CO2 to bicarbonate, with it k(cat) of 6.4 x 10(5) s(-1) and k(cat)/K-m of 3.9 x 10(7) M-1.s(-1). A panel of 38 sulfonamides and one sulfamate have been investigated for inhibition of this new beta-CA. All types of activities have been detected, with K(t)s in the range of 17 nM to 5.87 mu M. The best bsCA 1 inhibitors were ethoxzolamide (17 nM), celecoxib (18 nM), dorzolamide (21 nM), valdecoxib, and sulpiride (19 nM). Whether bsCA 1 inhibitors may have application in the Fight against brucellosis, an endemic disease and the major bacterial zoonosis, producing debilitating infection in humans and animals, warrants further studies.