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.

Related Concept Videos

Cholera01:25

Cholera

Cholera is an acute gastrointestinal disease caused by the Gram-negative bacterium Vibrio cholerae. It is transmitted primarily via the fecal-oral route through the ingestion of contaminated water or food.Vibrio cholerae is a motile, Gram-negative bacterium of the family Vibrionaceae, primarily associated with waterborne outbreaks in areas with inadequate sanitation. Although over 200 serogroups of V. cholerae exist, only O1 and O139 are responsible for epidemic cholera. The O1 serogroup,...
40
Common Ion Effect03:24

Common Ion Effect

Compared with pure water, the solubility of an ionic compound is less in aqueous solutions containing a common ion (one also produced by dissolution of the ionic compound). This is an example of a phenomenon known as the common ion effect, which is a consequence of the law of mass action that may be explained using Le Châtelier’s principle. Consider the dissolution of silver iodide:
48.0K
Titration of a Weak Base with a Strong Acid01:20

Titration of a Weak Base with a Strong Acid

The titration curve of a weak base like ammonia with a strong acid like hydrochloric acid is the mirror image of the titration curve of a weak acid with a strong base.
Using the ICE table and substituting the Kb value, we calculate the initial pH of 50 mL of 0.1 M ammonia to be 11.11. Addition of 25 mL of 0.1 M hydrochloric acid to this solution of ammonia results in a buffer with an equal concentration of ammonia and ammonium ions. The pH of this buffer can be calculated by substituting these...
9.4K
Estimation of k and VD of Aminoglycosides01:20

Estimation of k and VD of Aminoglycosides

Aminoglycosides are a class of antibiotics used to treat various bacterial infections. Clinicians must determine the elimination rate constant (k) and volume of distribution (VD) to optimize therapeutic efficacy and minimize toxicity. The k value represents the rate at which the drug is removed from the body, and the VD reflects the degree to which the drug distributes into body tissues. Accurately estimating these parameters allows healthcare professionals to tailor drug dosing to individual...
297
Enzyme Inhibition01:30

Enzyme Inhibition

Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.
94.8K
Bicarbonate-Carbonic Acid Buffer01:22

Bicarbonate-Carbonic Acid Buffer

The carbonic acid-bicarbonate buffer system is critical for maintaining the body's pH balance. It operates on the equilibrium:
7.5K