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Open AccessArticle

Cloning, Characterization and Anion Inhibition Studies of a β-Carbonic Anhydrase from the Pathogenic Protozoan Entamoeba histolytica

1
Faculty of Medicine and Health Technology, Tampere University, 33100 Tampere, Finland
2
Neurofarba Dept., Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze, Via U. Schiff 6, Sesto Fiorentino, 50019 Florence, Italy
3
Fimlab Ltd., Tampere University Hospital, 33100 Tampere, Finland
*
Author to whom correspondence should be addressed.
Molecules 2018, 23(12), 3112; https://doi.org/10.3390/molecules23123112
Received: 1 November 2018 / Revised: 27 November 2018 / Accepted: 27 November 2018 / Published: 28 November 2018
(This article belongs to the Special Issue Trends in the Development of Enzyme Inhibitors)
We report the cloning and catalytic activity of a β-carbonic anhydrase (CA, EC 4.2.1.1), isolated from the pathogenic protozoan Entamoeba histolytica, EhiCA. This enzyme has a high catalytic activity for the physiologic CO2 hydration reaction, with a kcat of 6.7 × 105 s−1 and a kcat/Km of 8.9 × 107 M−1 × s−1. An anion inhibition study of EhiCA with inorganic/organic anions and small molecules revealed that fluoride, chloride, cyanide, azide, pyrodiphosphate, perchlorate, tetrafluoroborate and sulfamic acid did not inhibit the enzyme activity, whereas pseudohalides (cyanate and thiocyanate), bicarbonate, nitrate, nitrite, diethyldithiocarbamate, and many complex inorganic anions showed inhibition in the millimolar range (KIs of 0.51–8.4 mM). The best EhiCA inhibitors were fluorosulfonate, sulfamide, phenylboronic acid and phenylarsonic acid (KIs in the range of 28–86 μM). Since β-CAs are not present in vertebrates, the present study may be useful for detecting lead compounds for the design of effective enzyme inhibitors, with potential to develop anti-infectives with alternative mechanisms of action. View Full-Text
Keywords: carbonic anhydrase; metalloenzymes; protozoan; Entamoeba histolytica; anions; inhibitor carbonic anhydrase; metalloenzymes; protozoan; Entamoeba histolytica; anions; inhibitor
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MDPI and ACS Style

Haapanen, S.; Bua, S.; Kuuslahti, M.; Parkkila, S.; Supuran, C.T. Cloning, Characterization and Anion Inhibition Studies of a β-Carbonic Anhydrase from the Pathogenic Protozoan Entamoeba histolytica. Molecules 2018, 23, 3112.

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