Electrostatic control of proton-transfer reaction in the active site of carbonic anhydrase

Abstract

The mechanism of proton-transfer (PT) in the active site (AS) of carbonic anhydrase was examined using ab initio calculations on geometry and electronic structure of model complex simulating PT system of the enzyme. The analysis of charge distribution on atoms of the complex gives evidence of the electrostatic control of the PT through H-bonded water chain connecting donor and acceptor groups. The PT reaction proceeds via the concerted mechanism in accordance with the principle of least dipole moment in transition state. The obtained results show that the electrostatic interaction in the enzyme AS can play the role of an ‘engine’ driving the delivery of a proton from donor to acceptor through the bridge waters. The mobility of the water molecules forming a proton channel is found to be crucial to the PT process.