title: Anion inhibition studies of a β-carbonic anhydrase from Clostridium perfringens.
abstract: A β-carbonic anhydrases (CAs, EC 4.2.1.1) was recently cloned, purified and characterized kinetically in the pathogen Clostridium perfringens. We report here the first inhibition study of this enzyme (CpeCA). CpeCA was poorly inhibited by iodide and bromide, and was inhibited with KIs in the range of 1-10mM by a range of anions such as (thio)cyanate, azide, bicarbonate, nitrate, nitrite, hydrogensulfite, hydrogensulfide, stannate, tellurate, pyrophosphate, divanadate, tetraborate, peroxydisulfate, sulfate, iminodisulfonate and fluorosulfonate. Better inhibitory power, with K(I)s of 0.36-1.0 mM, was observed for cyanide, carbonate, selenate, selenocyanide, trithiocarbonate and diethyldithiocarbamate, whereas the best CpeCA inhibitors were sulfamate, sulfamide, phenylboronic acid and phenylarsonic acid, which had KIs in the range of 7-75 μM. This study thus provides the basis for developing better clostridial enzyme inhibitors with potential as antiinfectives with a new mechanism of action.
authors.affiliation: Università degli Studi di Firenze, Chemistry Department, 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: R Siva
authors.initials: RS
authors.lastname: Sai Kumar
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.forename: Clemente
authors.initials: C
authors.lastname: Capasso
authors.forename: James G
authors.initials: JG
authors.lastname: Ferry
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000838:Anions / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000378:metabolism; D003016:Clostridium perfringens / Q000145:classification / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding / Q000187:drug effects; D016415:Sequence Alignment
chemical_list: D000838:Anions; D001426:Bacterial Proteins; D002257:Carbonic Anhydrase Inhibitors; D002256:Carbonic Anhydrases
keywords: Anion; Beta class enzyme; Carbonic anhydrase; Clostridium perfringens; Sulfonamide