title: Anion and sulfonamide inhibition studies of an α-carbonic anhydrase from the Antarctic hemoglobinless fish Chionodraco hamatus.
abstract: An α-carbonic anhydrase (CA, EC 4.2.1.1) has been purified from the Antarctic hemoglobinless fish Chionodraco hamatus (icefish). The new enzyme, denominated ChaCA, has a good catalytic activity for the physiologic CO2 hydration to bicarbonate reaction, similar to that of the low activity human isoform hCA I, with a kcat of 5.3×10(5) s(-1), and a kcat/Km of 3.7×10(7) M(-1) s(-1). The enzyme was inhibited in the submillimolar range by most inorganic anions (cyanate, thiocyanate, cyanide, bicarbonate, halides), whereas sulfamide, sulfamate, phenylboronic/phenylarsonic acids were micromolar inhibitors, with KIs in the range of 9-77 μM. Many clinically used drugs, such as acetazolamide, methazolamide, dorzolamide, brinzolamide, topiramate and benzolamide were low nanomolar inhibitors, with KIs in the range of 39.1-77.6 nM. As the physiology of CO2/bicarbonate transport or the Root effect in this Antarctic fish are poorly understood at this moment, such inhibition data may give a more detailed insight in the role that CAs play in these phenomena, by the use of inhibitors described here as physiologic tools.
authors.affiliation: Università degli Studi di Firenze, Dipartimento di Chimica Ugo Schiff, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cincinelli
authors.affiliation: Università degli Studi di Firenze, Dipartimento di Chimica Ugo Schiff, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.
authors.forename: Tania
authors.initials: T
authors.lastname: Martellini
authors.affiliation: Università degli Studi di Firenze, Dipartimento di Chimica Ugo Schiff, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
authors.affiliation: Università degli Studi di Firenze, Dipartimento di Chimica Ugo Schiff, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy; Università degli Studi di Firenze, Polo Scientifico, Dipartimento NEUROFARBA;Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Firenze), Italy. Electronic address: claudiu.supuran@unifi.it.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000818:Animals; D000838:Anions / Q000494:pharmacology; D000864:Antarctic Regions; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D002256:Carbonic Anhydrases / Q000302:isolation & purification* / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005399:Fishes / Q000502:physiology*; D015394:Molecular Structure; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000838:Anions; D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides; D002256:Carbonic Anhydrases
keywords: Anion; Carbonic anhydrase; Chionodraco hamatus; Sulfonamide