title: Carbonic anhydrase inhibitors: the beta-carbonic anhydrase from Helicobacter pylori is a new target for sulfonamide and sulfamate inhibitors.
abstract: DNA clones for the beta-class carbonic anhydrase (CA, EC 4.2.1.1) of Helicobactor pylori (hpbetaCA) were obtained. A recombinant hpbetaCA protein lacking the N-terminal 15-amino acid residues was produced and purified, representing a catalytically efficient CA. hpbetaCA was strongly inhibited (K(I)s in the range of 24-45 nM) by many sulfonamides/sulfamates, among which acetazolamide, ethoxzolamide, topiramate, and sulpiride, all clinically used drugs. The dual inhibition of alpha- and/or beta-class CAs of H. pylori might represent a useful alternative for the management of gastritis/gastric ulcers, as well as gastric cancer. This is also the first study showing that a bacterial beta-CA can be a drug target.
authors.affiliation: Department of Gastroenterology and Hepatology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Nishimori
authors.forename: Tomoko
authors.initials: T
authors.lastname: Minakuchi
authors.forename: Takuhiro
authors.initials: T
authors.lastname: Kohsaki
authors.forename: Saburo
authors.initials: S
authors.lastname: Onishi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
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; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003001:Cloning, Molecular; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D016480:Helicobacter pylori / Q000201:enzymology*; D006801:Humans; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013274:Stomach Neoplasms / Q000188:drug therapy; D013276:Stomach Ulcer / Q000188:drug therapy; D013449:Sulfonamides / Q000037:antagonists & inhibitors* / Q000737:chemistry*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; D013449:Sulfonamides; D002256:Carbonic Anhydrases