Carbonic anhydrase activators: Activation of the β-carbonic anhydrases from the pathogenic fungi Candida albicans and Cryptococcus neoformans with amines and amino acids

The proteins encoded by the Nce103 genes of Candida albicans and Cryptococcus neoformans are catalytically active β-carbonic anhydrases (CAs, EC 4.2.1.1) playing various roles in the life cycle of these fungal pathogens, such as CO2 sensing, regulation of capsule biosynthesis, filamentation, and adaptation of the organism to various pH and CO2 conditions in various niches where the fungi grow. Here, we report the first activation study of these two enzymes, CaNce103 and Can2, respectively, with amines and amino acids. The C. albicans enzyme, CaNce103 was activated by amino acids such as l-/d-His, l-d-Trp, l-Tyr with KAs in the range of 19.5–46 μM. More effective activators were some amines such as histamine, dopamine, 2-aminoethyl-piperazine, and l-adrenaline (KAs of 13.2–18.5 μM). The best CaNce103 activators were l- and d-Dopa, with KAs of 0.96–2.5 μM. The C. neoformans enzyme, Can2, showed much lower propensity to be activated by all these amino acids and amines, which had activation constants in the range of 28.7–47.2 μM. The best Can2 activator was l-Trp. This study may help to better understand the catalytic/activation mechanisms of the β-CAs and eventually to design CA activity modulators of such widespread enzymes in pathogenic fungi.

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