Anion inhibition studies of two new β-carbonic anhydrases from the bacterial pathogen Legionella pneumophila
| Autor: | Clemente Capasso, Zeid A. ALOthman, Daniela Vullo, Isao Nishimori, Sameh M. Osman, Andrea Scozzafava, Claudiu T. Supuran, Tomoko Minakuchi |
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| Rok vydání: | 2014 |
| Předmět: |
Anions
Clinical Biochemistry Molecular Conformation beta-Class enzyme Anion Pharmaceutical Science Biochemistry Legionella pneumophila Structure-Activity Relationship chemistry.chemical_compound Carbonic anhydrase Drug Discovery Enzyme kinetics Enzyme Inhibitors Phenylboronic acid Molecular Biology Sulfamide Carbonic Anhydrases chemistry.chemical_classification Dose-Response Relationship Drug Dithiocarbamate biology Organic Chemistry Phenylarsonic acid biology.organism_classification Enzyme chemistry biology.protein Molecular Medicine Azide |
| Zdroj: | Bioorganic & medicinal chemistry letters 24 (2014): 1127–1132. doi:10.1016/j.bmcl.2013.12.124 info:cnr-pdr/source/autori:Nishimori, Isao; Vullo, Daniela; Minakuchi, Tomoko; Scozzafava, Andrea; Osman, Sameh M.; AlOthman, Zeid; Capasso, Clemente; Supuran, Claudiu T./titolo:Anion inhibition studies of two new beta-carbonic anhydrases from the bacterial pathogen Legionella pneumophila/doi:10.1016%2Fj.bmcl.2013.12.124/rivista:Bioorganic & medicinal chemistry letters (Print)/anno:2014/pagina_da:1127/pagina_a:1132/intervallo_pagine:1127–1132/volume:24 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2013.12.124 |
| Popis: | We investigated the cloning, catalytic activity and anion inhibition of the beta-class carbonic anhydrases (CAs, EC 4.2.1.1) from the bacterial pathogen Legionella pneumophila. Two such enzymes, lpCA(1) and lpCA(2), were found in the genome of this pathogen. These enzymes were determined to be efficient catalysts for CO2 hydration, with k(cat) values in the range of (3.4-8.3) x 10(5) s(-1) and k(cat)/K-M values of (4.7-8.5) x 10(7) M-1 s(-1). A set of inorganic anions and small molecules was investigated to identify inhibitors of these enzymes. Perchlorate and tetrafluoroborate were not acting as inhibitors (K-I > 200 mM), whereas sulfate was a very weak inhibitor for both lpCA(1) and lpCA(2) (KI values of 77.9-96.5 mM). The most potent lpCA(1) inhibitors were cyanide, azide, hydrogen sulfide, diethyldithiocarbamate, sulfamate, sulfamide, phenylboronic acid and phenylarsonic acid, with K-I values ranging from 6 to 94 mu M. The most potent lpCA(2) inhibitors were diethyldithiocarbamate, sulfamide, sulfamate, phenylboronic acid and phenylarsonic acid, with K-I values ranging from 2 to 13 mu M. As these enzymes seem to be involved in regulation of phagosome pH during Legionella infection, inhibition of these targets may lead to antibacterial agents with a novel mechanism of action. (C) 2014 Elsevier Ltd. All rights reserved. |
| Databáze: | OpenAIRE |
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