title: Sulfonamide inhibition studies of the γ-carbonic anhydrase from the Antarctic cyanobacterium Nostoc commune.
abstract: A carbonic anhydrase (CA, EC 4.2.1.1) belonging to the γ-class has been cloned, purified and characterized from the Antarctic cyanobacterium Nostoc commune. The enzyme showed a good catalytic activity for the physiologic reaction (hydration of carbon dioxide to bicarbonate and a proton) with the following kinetic parameters, kcat of 9.5×10(5)s(-1) and kcat/KM of 8.3×10(7)M(-1)s(-1), being the γ-CA with the highest catalytic activity described so far. A range of aromatic/heterocyclic sulfonamides and one sulfamate were investigated as inhibitors of the new enzyme, denominated here NcoCA. The best NcoCA inhibitors were some sulfonylated sulfanilamide derivatives possessing elongated molecules, aminobenzolamide, acetazolamide, benzolamide, dorzolamide, brinzolamide and topiramate, which showed inhibition constants in the range of 40.3-92.3nM. As 1,5-bisphosphate carboxylase/oxygenase (RubisCO) and γ-CAs are closely associated in carboxysomes of cyanobacteria for enhancing the affinity of RubisCO for CO2 and the efficiency of photosynthesis, investigation of this new enzyme and its affinity for modulators of its activity may bring new insights in these crucial processes.
authors.affiliation: Università degliStudi di Firenze, Dipartimento Di Chimica, Laboratorio di ChimicaBioinorganica, Polo Scientifico, Via della Lastruccia3, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
authors.affiliation: Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 81, Napoli, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: De Luca
authors.affiliation: Università degliStudi di Firenze, Dipartimento Di Chimica, Laboratorio di ChimicaBioinorganica, Polo Scientifico, Via della Lastruccia3, 50019 Sesto Fiorentino, Florence, Italy; Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 81, Napoli, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Del Prete
authors.affiliation: Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 81, Napoli, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Carginale
authors.affiliation: Università degliStudi di Firenze, Dipartimento Di Chimica, Laboratorio di ChimicaBioinorganica, Polo Scientifico, Via della Lastruccia3, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.affiliation: Istituto di Bioscienze e Biorisorse, CNR, Via Pietro Castellino 81, Napoli, Italy. Electronic address: clemente.capasso@ibbr.cnr.it.
authors.forename: Clemente
authors.initials: C
authors.lastname: Capasso
authors.affiliation: Università degliStudi di Firenze, Dipartimento Di Chimica, Laboratorio di ChimicaBioinorganica, Polo Scientifico, Via della Lastruccia3, 50019 Sesto Fiorentino, Florence, Italy; Università degliStudi di Firenze, DipartimentoNeurofarba, Sezione di ScienzeFarmaceutiche, Polo Scientifico, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy. Electronic address: claudiu.supuran@unifi.it.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000595:Amino Acid Sequence; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D050501:Nostoc commune / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology*; D016415:Sequence Alignment; D000077145:Sulfanilamide; D013424:Sulfanilamides / Q000737:chemistry / Q000494:pharmacology; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology*; D013843:Thiazines / Q000737:chemistry / Q000494:pharmacology; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D013424:Sulfanilamides; D013449:Sulfonamides; D013843:Thiazines; D013876:Thiophenes; D000077145:Sulfanilamide; C111827:brinzolamide; C062765:dorzolamide; D002256:Carbonic Anhydrases
keywords: Antarctic carbonic anhydrase; Carbonic anhydrase; Cyanobacteria; Hydratase activity; Metalloenzymes