Anion inhibition studies of a β-carbonic anhydrase from Clostridium perfringens
| Autor: | Andrea Scozzafava, James G. Ferry, Daniela Vullo, Claudiu T. Supuran, Clemente Capasso, R. Siva Sai Kumar |
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| Rok vydání: | 2013 |
| Předmět: |
Anions
Fluorosulfonate Clostridium perfringens Bicarbonate Molecular Sequence Data Clinical Biochemistry Pharmaceutical Science medicine.disease_cause Biochemistry Medicinal chemistry Pyrophosphate chemistry.chemical_compound Bacterial Proteins Carbonic anhydrase Drug Discovery medicine Animals Humans Organic chemistry Amino Acid Sequence Carbonic Anhydrase Inhibitors Molecular Biology Phylogeny Sulfamide Carbonic Anhydrases biology Organic Chemistry Phenylarsonic acid Cyanate Enzyme Activation Kinetics chemistry biology.protein Molecular Medicine Sequence Alignment Protein Binding |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 23:6706-6710 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2013.10.037 |
| Popis: | 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 K I s in the range of 1–10 mM 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 K I s 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. |
| Databáze: | OpenAIRE |
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