title: The extremo-α-carbonic anhydrase from the thermophilic bacterium Sulfurihydrogenibium azorense is highly inhibited by sulfonamides.
abstract: The α-carbonic anhydrase (CA, EC 4.2.1.1) from the newly discovered extremophilic bacterium Sulfurihydrogenibium azorense (SazCA) is the most effective CA known to date. Here we investigated the inhibition profile of this enzyme with a series of aromatic and heterocyclic sulfonamides, and one sulfamate. Many clinically used sulfonamides, such as acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, topiramate, celecoxib and sulpiride were low nanomolar/subnanomolar SazCA inhibitors (KIs in the range of 0.9-10.8 nM) whereas simple aromatic derivatives were less effective as SazCA inhibitors. The inhibition profile of SazCA is slightly different from that of the related enzyme from S. yellostonense (SspCA), investigated earlier by our groups.
authors.affiliation: Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
authors.forename: Viviana
authors.initials: V
authors.lastname: De Luca
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Carginale
authors.forename: Mosè
authors.initials: M
authors.lastname: Rossi
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; D001419:Bacteria / Q000187:drug effects* / Q000201:enzymology*; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides; D002256:Carbonic Anhydrases