Activation Studies of the β-Carbonic Anhydrase from the Pathogenic Protozoan Entamoeba histolytica with Amino Acids and Amines

Silvia Bua; Susanna Haapanen; Marianne Kuuslahti; Seppo Parkkila; Claudiu T Supuran

doi:10.3390/metabo9020026

Activation Studies of the β-Carbonic Anhydrase from the Pathogenic Protozoan Entamoeba histolytica with Amino Acids and Amines

Metabolites. 2019 Feb 1;9(2):26. doi: 10.3390/metabo9020026.

Authors

Silvia Bua¹, Susanna Haapanen², Marianne Kuuslahti³, Seppo Parkkila^{4

5}, Claudiu T Supuran⁶

Affiliations

¹ Sezione di Scienze Farmaceutiche e Nutraceutiche, Dipartimento Neurofarba, Università degli Studi di Firenze, Via U. Schiff 6, 50019 Sesto Fiorentino, 50019 Florence, Italy. silvia.bua@unifi.it.
² Faculty of Medicine and Health Technology, Tampere University, 33100 Tampere, Finland. Haapanen.Susanna.E@student.uta.fi.
³ Faculty of Medicine and Health Technology, Tampere University, 33100 Tampere, Finland. Marianne.Kuuslahti@staff.uta.fi.
⁴ Faculty of Medicine and Health Technology, Tampere University, 33100 Tampere, Finland. seppo.parkkila@staff.uta.fi.
⁵ Fimlab Ltd., Tampere University Hospital, 33100 Tampere, Finland. seppo.parkkila@staff.uta.fi.
⁶ Sezione di Scienze Farmaceutiche e Nutraceutiche, Dipartimento Neurofarba, Università degli Studi di Firenze, Via U. Schiff 6, 50019 Sesto Fiorentino, 50019 Florence, Italy. claudiu.supuran@unifi.it.

Abstract

The β-carbonic anhydrase (CA, EC 4.2.1.1) from the pathogenic protozoan Entamoeba histolytica, EhiCA, was investigated for its activation with a panel of natural and non-natural amino acids and amines. EhiCA was potently activated by D-His, D-Phe, D-DOPA, L- and D-Trp, L- and D-Tyr, 4-amino-L-Tyr, histamine and serotonin, with K_As ranging between 1.07 and 10.1 M. The best activator was D-Tyr (K_A of 1.07 µM). L-Phe, L-DOPA, L-adrenaline, L-Asn, L-Asp, L-Glu and L-Gln showed medium potency activation, with K_As of 16.5⁻25.6 µM. Some heterocyclic- alkyl amines, such as 2-pyridyl-methyl/ethyl-amine and 4-(2-aminoethyl)-morpholine, were devoid of EhiCA activating properties with K_As > 100 µM. As CA activators have poorly been investigated for their interaction with protozoan CAs, our study may be relevant for an improved understanding of the role of this enzyme in the life cycle of E. histolytica.

Keywords: Entamoeba histolytica; activator; amine; amino acid; carbonic anhydrase; metalloenzymes; protozoan.