title: Inhibition studies of a beta-carbonic anhydrase from Brucella suis with a series of water soluble glycosyl sulfanilamides.
abstract: A beta-carbonic anhydrase (CA, EC 4.2.1.1) from the bacterial pathogen Brucella suis, bsCA 1, has been cloned, purified characterized kinetically and for inhibition with a series of water soluble glycosylated sulfanilamides. bsCA 1 has appreciable activity as catalyst for the hydration of CO(2) to bicarbonate, with a k(cat) of 6.4x10(5) s(-1) and k(cat)/K(m) of 3.9x10(7) M(-1) s(-1). All types of inhibitory activities have been detected, with K(I)s in the range of 8.9-110 nM. The best bsCA 1 inhibitor were the galactose and ribose sulfanilamides, with inhibition constants of 8.9-9.2 nM. Small structural changes in the sugar moiety led to dramatic differences of enzyme inhibitory activity for this series of compounds. One of the tested glycosylsulfonamides and acetazolamide significantly inhibited the growth of the bacteria in cell cultures.
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: Isao
authors.initials: I
authors.lastname: Nishimori
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.forename: Stephan
authors.initials: S
authors.lastname: Köhler
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Winum
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000595:Amino Acid Sequence; D041021:Brucella suis / Q000201:enzymology*; D002241:Carbohydrates / Q000737:chemistry; D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D013424:Sulfanilamides / Q000737:chemistry* / Q000494:pharmacology*; D014867:Water / Q000737:chemistry
chemical_list: D002241:Carbohydrates; D002257:Carbonic Anhydrase Inhibitors; D013424:Sulfanilamides; D014867:Water; D024401:Carbonic Anhydrase I