Inhibition studies of a β-carbonic anhydrase from Brucella suis with a series of water soluble glycosyl sulfanilamides |
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| Authors: | Daniela Vullo Isao Nishimori Andrea Scozzafava Stephan Köhler Jean-Yves Winum Claudiu T Supuran |
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| Institution: | 1. Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy;2. Department of Gastroenterology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan;3. Centre d’Etudes d’Agents Pathogènes et Biotechnologies pour la Santé (CPBS), UMR 5236, Université Montpellier I, and CNRS, Université Montpellier II, cc100, Place E. Bataillon, 34095 Montpellier, France;4. Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS-UM1-UM2, Bâtiment de Recherche Max Mousseron, Ecole Nationale Supérieure de Chimie de Montpellier, 8 rue de l’Ecole Normale, 34296 Montpellier Cedex, France |
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| Abstract: | A β-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 CO2 to bicarbonate, with a kcat of 6.4 × 105 s?1 and kcat/Km of 3.9 × 107 M?1 s?1. All types of inhibitory activities have been detected, with KIs 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. |
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