Carbonic anhydrase ligand-binding sites

The 2.0 A electron density map of carboxypeptidase A shows three zinc-protein contacts (91). The ligands have been identified as histidine-69, glutamic acid-72 and histidine-196 (91, 101), where the numbers indicate the positions of the residues in the sequence counted from the N-terminal end. The geometry of the complex is irregular but resembles a distorted tetrahedron with an open position directed towards the active site pocket, and presumably occupied by water in the resting enzyme (91). The similarity with the tentative structure of the metal-binding site in carbonic anhydrase is striking. 

The catalytic mechanism for C02 hydration-dehydration by carbonic anhydrase represents the focal issue of the present discussion. We have to consider two aspects (1) the mode of binding of the C02 substrate at the active site, and (2) the physical-chemical state of ligands on the zinc ion. 

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