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Published on: May 30, 2017
Anion inhibition studies of the β-carbonic anhydrase from the pathogenic bacterium Vibrio cholerae
Daniela Vullo1, Sonia Del Prete2, Viviana De Luca3
1Università degli Studi di Firenze, Dipartimento Di Chimica, Laboratorio di Chimica Bioinorganica, Polo Scientifico, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
Insights
Researchers investigated inhibitors for Vibrio cholerae beta-carbonic anhydrase (VchCAβ). Sulfamide and phenylboronic acid were potent inhibitors, offering potential for new antimicrobial drug development.
Area of Science:
- Biochemistry
- Microbiology
- Enzymology
Background:
- Vibrio cholerae, a pathogen, possesses three carbonic anhydrase (CA) enzymes.
- Carbonic anhydrases are crucial metalloenzymes involved in various physiological processes.
Purpose of the Study:
- To investigate the anion inhibition of the beta-class carbonic anhydrase from Vibrio cholerae (VchCAβ).
- To identify potential selective inhibitors of VchCAβ for pharmacological applications.
Main Methods:
- Anion inhibition studies were performed on purified VchCAβ.
- Enzyme kinetics were used to determine inhibition constants (KIs).
Main Results:
- Sulfamide, sulfamate, phenylboronic acid, and phenylarsonic acid were identified as potent VchCAβ inhibitors (KIs: 54-86 μM).
- Diethyldithiocarbonate showed moderate inhibition (KI: 0.73 mM).
- Various other anions exhibited inhibition in the millimolar range.
Conclusions:
- Selective VchCAβ inhibitors were identified, distinct from human CA isoforms.
- These inhibitors could serve as valuable tools for studying VchCAβ's physiological roles and for developing novel therapeutics.
Abstract:
The genome of the pathogenic bacterium Vibrio cholerae encodes for three carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the α-, β- and γ-classes. Here we report and anion inhibition study of the β-CA, VchCAβ with anions and other small molecules which inhibit metalloenzymes. The best VchCAβ anion inhibitors were sulfamide, sulfamate, phenylboronic acid and phenylarsonic acid, which showed KIs in the range of 54-86μM. Diethyldithiocarbonate was also an effective VchCAβ inhibitor, with an inhibition constant of 0.73mM. The halides, cyanate, thiocyanate, cyanide, bicarbonate, carbonate, nitrate, nitrite, stannate, selenate, tellurate, divanadate, tetraborate, perrhenate, perruthenate, peroxydisulfate, selenocyanide, trithiocarbonate, and fluorosulfonate showed affinity in the low millimolar range, with KIs of 2.3-9.5mM. Identification of selective inhibitors of VchCAβ (over the human CA isoforms) may lead to pharmacological tools useful for understanding the physiological role(s) of this under-investigated enzyme.
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