Carbonic Anhydrase Inhibitors. Cloning, Characterization, and Inhibition Studies of a New β-Carbonic Anhydrase from Mycobacterium tuberculosis

The Rv3273 gene product of Mycobacterium tuberculosis, beta-carbonic anhydrase (CA, EC 4.2.1.1), mtCA 3, shows appreciable catalytic activity for CO2 hydration (k(cat) of 4.3 x 10(5) s(-1), and k(cat)/K-m of 4.0 x 10(7) M-1.s(-1)). A series of sulfonamides/sulfamates was assayed for their interaction with mtCA 3. Sulfanilyl-sulfonamides, acetazolamide, methazolamide, ethoxzolamide; dichlorophenamide, dorzolamide, brinzolamide, benzolamide, and zonisamide, showed effective, submicromolar inhibition (K(I)s of 104-611 nM), the best inhibitor being 2-amino-pyrimidin-4-yl-sulfanilamide (K-I of 91 nM).