Density functional theory investigations of the catalytic mechanism of β-carbonic anhydrase

Carbonic anhydrase (CA) is an enzyme that catalyses the reversible hydration of carbon dioxide. There are three broad classes α, β, and γ, of CA, divided into three genetically unrelated families, namely, animal, plant, and bacterial CAs, respectively. The active site of this enzyme contains a zinc atom which is necessary for catalysis. In this study, the catalytic mechanism of β-CA has been investigated using its active site model employing DFT based Becke’s three parameter exchange and B3LYP method. It is evident from the results that the activation barrier for the nucleophilic attack is negligible, which is similar to that of α-CA. Furthermore, results show that Asp162-Arg164 dyad and Glu151 residues play a decisive role in the catalysis. Primarily, the catalytic dyad orients the hydroxyl group appropriately to enable nucleophilic attack and stabilizes the negative charge on the bicarbonate.