title: Anion inhibition studies of the α-carbonic anhydrase from the pathogenic bacterium Vibrio cholerae.
abstract: An α-carbonic anhydrase (CA, EC 4.2.1.1) has been recently cloned and characterized in the human pathogenic bacterium Vibrio cholerae, denominated VchCA (Del Prete et al. J. Med. Chem.2012, 55, 10742). This enzyme shows a good catalytic activity for the CO2 hydration reaction, comparable to that of the human (h) isoform hCA I. Many inorganic anions and several small molecules were investigated as VchCA inhibitors. Inorganic anions such as cyanate, cyanide, hydrogen sulfide, hydrogen sulfite, and trithiocarbonate were effective VchCA inhibitors with inhibition constants in the range of 33-88μM. Other effective inhibitors were diethyldithiocarbamate, sulfamide, sulfamate, phenylboronic acid and phenylarsonic acid, with KIs of 7-43μM. Halides (bromide, iodide), bicarbonate and carbonate were much less effective VchCA inhibitors, with KIs in the range of 4.64-28.0mM. The resistance of VchCA to bicarbonate inhibition may represent an evolutionary adaptation of this enzyme to living in an environment rich in this ion, such as the gastrointestinal tract, as bicarbonate is a virulence enhancer of this bacterium.
authors: Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino, Firenze, Italy.
authors: Daniela
authors: D
authors: Vullo
authors: Semra
authors: S
authors: Isik
authors: Sonia
authors: S
authors: Del Prete
authors: Viviana
authors: V
authors: De Luca
authors: Vincenzo
authors: V
authors: Carginale
authors: Andrea
authors: A
authors: Scozzafava
authors: Claudiu T
authors: CT
authors: Supuran
authors: Clemente
authors: C
authors: Capasso
mesh_terms: D000838:Anions / Q000737:chemistry* / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D014734:Vibrio cholerae / Q000201:enzymology*
chemical_list: D000838:Anions; D002257:Carbonic Anhydrase Inhibitors; D020033:Protein Isoforms; D002245:Carbon Dioxide; D002256:Carbonic Anhydrases