Carbonic anhydrase activators: Activation of the archaeal β-class (Cab) and γ-class (Cam) carbonic anhydrases with amino acids and amines

Activation of the archaeal β-class (Cab) and γ-class (Cam) carbonic anhydrases (CAs, EC 4.2.1.1) with a series of natural and non-natural amino acids and aromatic/heterocyclic amines has been investigated. Cab, Zn-Cam and Co-Cam showed an activation profile with natural, l- and d-amino acids very different of those of the α-class enzymes CA I, II and III. Most of these compounds showed medium efficacy as archaeal CA activators, except for d-Phe and l-Tyr which were effective Cab activators (KAs of 10.3-10.5 μM), 2-pyridylmethylamine and 1-(2-aminoethyl)-piperazine which effectively activated Zn-Cam (KAs of 10.1-11.4 μM) and serotonin, l-adrenaline and 2-pyridylmethylamine which were the best Co-Cam activators (KAs of 0.97-8.9 μM). We prove here that the activation mechanisms of the α-, β-, and γ-class CAs are similar, although the activation profiles with various compounds differ dramatically between these diverse enzymes.