Sulfonamide inhibition profiles of the β-carbonic anhydrase from the pathogenic bacterium Francisella tularensis responsible of the febrile illness tularemia
Del Prete S, Vullo D, Osman SM, Alothman Z, Supuran CT, Capasso C
A new (3-class carbonic anhydrase (CA, EC 4.2.1.1) has been cloned, purified and characterized in the genome of the pathogenic bacterium Francisella tularensis responsible of the febrile illness tularemia. This enzyme, FtuilCA, showed a kcal of 9.8 x 10(5) s(-1) and a kcac/KM of 8.9 x 10(7) M-1 s(-1) for the CO2 hydration, physiological reaction, being one of the most effective p-CAs known to date, with a catalytic activity only 1.68-times lower than that of the human(h) isoform hCA II. A panel of 39 simple aromatic and heterocyclic sulfonamides, as well as clinically used drugs incorporating sulfonamide/sulfamate zinc-binding groups, was used to investigate the inhibition profile of Ftu beta CA with these classes of derivatives. The enzyme generally showed a weaker affinity for these inhibitors compared to other alpha- and beta-CAs investigated earlier, with only acetazolamide and its deacetylated precursor having inhibition constant