Density functional theory study of proton transfer in carbonic anhydrase

Proton transfer in carbonic anhydrase II has been studied at the B3LYP/6-31G(D) level. The active site model consists of the zinc ion, four histidine residues, two threonine residues, and three water molecules. Our calculations showed that the proton of the zinc-bound water molecule could be transferred to the nearest water molecule and an intermediate containing H₃O⁺ is then formed. The intermediate is only 1.3 kJ·mol^−1 above the reactant complex, whereas the barrier height for the proton transfer is about 8.1 kJ·mol^−1.