title: The alpha-carbonic anhydrase from the thermophilic bacterium Sulfurihydrogenibium yellowstonense YO3AOP1 is highly susceptible to inhibition by sulfonamides.
abstract: The α-carbonic anhydrase (CA, EC 4.2.1.1) from the newly discovered thermophilic bacterium Sulfurihydrogenibium yellowstonense YO3AOP1 (SspCA) was investigated for its inhibition with a large series of sulfonamides and a sulfamate, the classical inhibitors of these zinc enzymes. SspCA showed an inhibition profile with these compounds very similar to that of the predominant human cytosolic isoform hCA II, and not to that of the bacterial α-CA from Helicobacter pylori. Some clinically used drugs such as acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, topiramate, celecoxib and sulthiame were low nanomolar SspCA/hCA II inhibitors (KIs in the range of 4.5-12.3nM) whereas simple aromatic/heterocyclic sulfonamides were less effective, micromolar inhibitors. As this highly catalytically active and thermostable enzyme may show biotechnological applications, its inhibition studies may be relevant for designing on/off systems to control its activity.
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 De
authors.initials: VD
authors.lastname: 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 / Q000201:enzymology*; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D016415:Sequence Alignment; D013449:Sulfonamides / Q000737:chemistry* / Q000378:metabolism
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D011994:Recombinant Proteins; D013449:Sulfonamides; D002256:Carbonic Anhydrases