DNA cloning, characterization, and inhibition studies of an alpha-carbonic anhydrase from the pathogenic bacterium Vibrio cholerae.
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Del Prete S, Isik S, Vullo D, De Luca V, Carginale V, Scozzafava A, Supuran CT, Capasso C
DNA cloning, characterization, and inhibition studies of an alpha-carbonic anhydrase from the pathogenic bacterium Vibrio cholerae.
J Med Chem. 2012 Dec 13;55(23):10742-8. doi: 10.1021/jm301611m. Epub 2012 Dec 4.
- PubMed ID
- 23181552 [ View in PubMed]
- Abstract
We have cloned, purified, and characterized an alpha-carbonic anhydrase (CA, EC 4.2.1.1) from the human pathogenic bacterium Vibrio cholerae, VchCA. The new enzyme has significant catalytic activity, and an inhibition study with sulfonamides and sulfamates led to the detection of a large number of low nanomolar inhibitors, among which are methazolamide, acetazolamide, ethoxzolamide, dorzolamide, brinzolamide, benzolamide, and indisulam (KI values in the range 0.69-8.1 nM). As bicarbonate is a virulence factor of this bacterium and since ethoxzolamide was shown to inhibit the in vivo virulence, we propose that VchCA may be a target for antibiotic development, exploiting a mechanism of action rarely considered until now.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Celecoxib Carbonic anhydrase 2 Ki (nM) 21 N/A N/A Details Sulthiame Carbonic anhydrase 2 Ki (nM) 9 N/A N/A Details Valdecoxib Carbonic anhydrase 2 Ki (nM) 43 N/A N/A Details