Thermodynamic study of proton transfer in carbonic anhydrase/activator complex: A quantum mechanical approach

Activation mechanism of human carbonic anhydrase (hCA) isoform II, with l-histidine and histamine has been investigated by using quantum mechanical calculations. Two methods including B3LYP/6-31G* and B3PW91/def2-SVP have been employed to calculate the details of electronic structure and electronic energy of active and inactive forms of carbonic anhydrase enzyme active center, isoform II (CA). Two activators of this enzyme including histamine and l-histidine and complex between these activators and active center of carbonic anhdrase have been investigated. Also thermodynamic functions for the total reaction and for the complexation between activators and CA are evaluated. The calculated results indicate that protonatable moiety of histidine and histamine molecules participate in proton transfer from zinc-bound water molecule and lead to formation of the catalytically active species of CA enzyme, hydroxide coordinated to the zinc ion. In all calculations, solvent effects have been considered in water using PCM method.