Cloning, characterization, and inhibition studies of a beta-carbonic anhydrase from Brucella suis.

Pascale Joseph, François Turtaut, Safia Ouahrani-Bettache, Jean-Louis Montero, Isao Nishimori, Tomoko Minakuchi, Daniela Vullo, Andrea Scozzafava, Stephan Köhler, Jean-Yves Winum, Claudiu T Supuran

Index: J. Med. Chem. 53 , 2277-85, (2010)

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Abstract

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 1 has appreciable activity as catalyst for the hydration of CO(2) to bicarbonate, with a 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(I)s in the range of 17 nM to 5.87 microM. 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.