title: DNA cloning, characterization, and inhibition studies of an α-carbonic anhydrase from the pathogenic bacterium Vibrio cholerae.
abstract: We have cloned, purified, and characterized an α-carbonic anhydrase (CA, EC 4.2.1.1) from the human pathogenic bacterium Vibrio cholerae, VchCA. The new enzyme has significant catalytic activity, and an inhibition study with sulfonamides and sulfamates led to the detection of a large number of low nanomolar inhibitors, among which are methazolamide, acetazolamide, ethoxzolamide, dorzolamide, brinzolamide, benzolamide, and indisulam (KI values in the range 0.69-8.1 nM). As bicarbonate is a virulence factor of this bacterium and since ethoxzolamide was shown to inhibit the in vivo virulence, we propose that VchCA may be a target for antibiotic development, exploiting a mechanism of action rarely considered until now.
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: Semra
authors.initials: S
authors.lastname: Isik
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; D055162:Biocatalysis; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D002256:Carbonic Anhydrases / Q000737:chemistry / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D008969:Molecular Sequence Data; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D014734:Vibrio cholerae / Q000201:enzymology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D004247:DNA; D002256:Carbonic Anhydrases