PROTON TRANSFER IN THE ENZYME CARBONIC ANHYDRASE : AN AB INITIO STUDY

Ab initio calculations have been performed to probe possible proton-transfer pathways in carbonic anhydrase. It is found that the proton transfer in the dehydration direction involves an energy barrier of around 8−10 kcal/mol, which agrees well with experiment, while the proton-transfer barrier in the hydration (away from zinc) direction is sensitive to the histidine ligand bonding around the Zn ion. The water ligand dependence of the proton-transfer energy barrier reveals a requirement of certain hydrogen bond formation in the active site. Preliminary studies involving two and three proton transfers through hydrogen-bonded water chains show that the donor−acceptor distance and the water chain motion are crucial to the proton-transfer energetics. On the basis of these results, a picture of the proton-transfer energetics and mechanism is presented and the effect of the His-64 ligand on the process is discussed.