The role of metal ions in the mechanism of action of hydrolytic metalloenzymes: Carbonic anhydrase

Abstract

Metalloenzymes are among the most efficient enzymes. One of the mechanisms available to hydrolytic metalloenzymes consists of using the metal ion, which is embedded in the protein, as a carrier for hydroxide ions in neutral solution. Models for this mechanism are surveyed and analyzed from the point of view of the “charge effect”. The active center of carbonic anhydrase is compared to several of these models, and the similarities are pointed out. It is concluded that the “carrier for hydroxide ions” mechanism is the most plausible one for carbonic anhydrase. It is proposed that the metal ion also plays a role in the regeneration of the active center of the enzyme, i.e. the ionization of the metal-bound water molecule, after each turnover. Some general implications for the mechanism of action of other hydrolytic metalloenzymes are considered.