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ID: ALA2401680

Journal: Bioorg Med Chem Lett

Title: A highly catalytically active γ-carbonic anhydrase from the pathogenic anaerobe Porphyromonas gingivalis and its inhibition profile with anions and small molecules.

Authors: Del Prete S, Vullo D, De Luca V, Carginale V, Scozzafava A, Supuran CT, Capasso C.

Abstract: Carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the γ-class are present in archaea, bacteria and plants but, except the Methanosarcina thermophila enzymes CAM and CAMH, they were poorly characterized so far. Here we report a new such enzyme (PgiCA), the γ-CA from the oral cavity pathogenic bacterium Porphyromonas gingivalis, the main causative agent of periodontitis. PgiCA showed a good catalytic activity for the CO2 hydration reaction, comparable to that of the human (h) isoform hCA I. Inorganic anions such as thiocyanate, cyanide, azide, hydrogen sulfide, sulfamate and trithiocarbonate were effective PgiCA inhibitors with inhibition constants in the range of 41-97 μM. Other effective inhibitors were diethyldithiocarbamate, sulfamide, and phenylboronic acid, with KIs of 4.0-9.8 μM. The role of this enzyme as a possible virulence factor of P. gingivalis is poorly understood at the moment but its good catalytic activity and the possibility to be inhibited by a large number of compounds may lead to interesting developments in the field.

CiteXplore: 23769640

DOI: 10.1016/j.bmcl.2013.05.063