Histidine reaction with carbon dioxide

This is of relevance to the mechanism of carbonic anhydrase. This enzyme, which catalyzes the hydration of C02, has at its active site a Zn2+ ion ligated to the imidazole rings of three of its histidines. The classic mechanism for the reaction is that the fourth ligand is a water molecule which ionizes with a pKa of 7.37 The reactive species is considered to be the zinc-bound hydroxyl. Chemical studies show that zinc-bound hydroxyls are no exception to the rule of high reactivity. The H20 in structure 2.31 ionizes with a pKa of 8.7 and catalyzes the hydration of carbon dioxide and acetaldehyde.38... 

The enzyme carbonic anhydrase catalyzes the conversion of carbon dioxide into bicarbonate ion (Section 1.20). It is a metalloenzyme, with Zn coordinated at the active site by three histidine residues. Propose a mechanism for this reaction. 

The action of red cell carbonic anhydrase I is a hydration reaction in which carbon dioxide and water interconvert with a bicarbonate ion and a hydrogen ion. The crystal structure [97, 98] reveals a molecule folded mainly with -pleated sheet (10 strands, some parallel and some antiparallel) together with seven a-helices. The active site is in a cavity in the center of the molecule. The crystal structure of the enzyme with bound aurocyanide shows the Zn(II) is coordinated to three histidine... 

Carbamic acids (RNHCOOH) appear to be fairly strong acids with estimated pK values in the neighborhood of 6.8 (174).It is also known that the carbamate reaction is a strongly exothermic one, having a heat of the order of 20,000 cal./mole (130, 174). Apparently the reaction is limited to aliphatic amines at any rate it does not take place with the NH group of histidine (176). In accordance with these considerations the expression for the equilibrium between an amine (RNHj) and carbon dioxide may be formulated on the basis of simple mass law considerations. To do so, we introduce the following definitions and equations ... 

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