title: Inhibition studies with anions and small molecules of two novel β-carbonic anhydrases from the bacterial pathogen Salmonella enterica serovar Typhimurium.
abstract: Two new β-carbonic anhydrases (CAs, EC 4.2.1.1) from the bacterial pathogen Salmonella enterica serovar Typhimurium, stCA 1 and stCA 2, were characterized kinetically. The two enzymes possess appreciable activity as catalysts for the hydration of CO(2) to bicarbonate, with k(cat) of 0.79×10(6) s(-1) and 1.0×10(6) s(-1), and k(cat)/K(m) of 5.2×10(7) M(-1) s(-1) and of 8.3×10(7) M(-1) s(-1), respectively. A large number of simple/complex inorganic anions as well as other small molecules (sulfamide, sulfamic acid, phenylboronic acid, phenylarsonic acid, dialkyldithiocarbamates) showed interesting inhibitory properties towards the two new enzymes, with several low micromolar inhibitors discovered. As many strains of S. enterica show extensive resistance to classical antibiotics, inhibition of the β-CAs investigated here may be useful for developing lead compounds for novel types of antibacterials.
authors.affiliation: Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Sesto Fiorentino (Florence), Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
authors.forename: Isao
authors.initials: I
authors.lastname: Nishimori
authors.forename: Tomoko
authors.initials: T
authors.lastname: Minakuchi
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000595:Amino Acid Sequence; D000838:Anions / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D008969:Molecular Sequence Data; D012486:Salmonella typhimurium / Q000201:enzymology*; D016415:Sequence Alignment
chemical_list: D000838:Anions; D002257:Carbonic Anhydrase Inhibitors; D002256:Carbonic Anhydrases