title: A highly catalytically active γ-carbonic anhydrase from the pathogenic anaerobe Porphyromonas gingivalis and its inhibition profile with anions and small molecules.
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.
authors.affiliation: Istituto di Biochimica delle Proteine - CNR, Via P. Castellino 111, 80131 Napoli, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Del Prete
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
authors.forename: Viviana
authors.initials: V
authors.lastname: De Luca
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Carginale
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
authors.forename: Clemente
authors.initials: C
authors.lastname: Capasso
mesh_terms: D000595:Amino Acid Sequence; D000838:Anions / Q000737:chemistry* / Q000378:metabolism; D055162:Biocatalysis; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D002256:Carbonic Anhydrases / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D010802:Phylogeny; D016966:Porphyromonas gingivalis / Q000201:enzymology*; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D000838:Anions; D002257:Carbonic Anhydrase Inhibitors; D020033:Protein Isoforms; D002256:Carbonic Anhydrases