Activation studies with amines and amino acids of the β-carbonic anhydrase from the pathogenic protozoan Leishmania donovani chagasi

The activation of a β-class carbonic anhydrase (CAs, EC 4.2.1.1) from Leishmania donovani chagasi (LdcCA) was investigated using a panel of natural and non-natural amino acids and amines. The most effective activators belonged to the amine class, with histamine, dopamine, serotonin, 2-pyridyl-methylamine and 4-(2-aminoethyl)-morpholine with activation constants in the range of 0.23-0.94 µM. In addition, 2-(2-aminoethyl)pyridine and 1-(aminoethyl)-piperazine were even more effective activators (KAs of 9-12 nM). Amino acids such as L-/D-His, L-/D-Phe, L-/D-DOPA, L-/D-Trp and L-/D-Tyr were slightly less effective activators compared to the amines, but showed activation constants in the low micromolar range (1.27-9.16 µM). Many of the investigated activators are autacoids that are present in rather high concentrations in different tissues of the host mammals infected by these parasites. As CA activators have not yet been investigated for protozoan CAs, this study may be relevant for an improved understanding of the role of this enzyme in the life cycle of Leishmania.