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What is the role of the metal ion in the active site of the metalloenzyme carbonic anhydrase, and how does this facilitate the enzyme's function of catalyzing the hydration of carbon dioxide to bicarbonate ion?

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Carbonic anhydrase is a metalloenzyme that plays a crucial role in the reversible hydration of carbon dioxide  CO2  to bicarbonate ion  HCO3-  and a proton  H+ . The metal ion in the active site of carbonic anhydrase is typically zinc  Zn2+ , which is essential for the enzyme's catalytic activity.The role of the metal ion  Zn2+  in the active site of carbonic anhydrase can be described in the following steps:1. Coordination: The Zn2+ ion is coordinated to three histidine residues in the enzyme's active site, forming a distorted tetrahedral geometry. The fourth coordination site is occupied by a water molecule  H2O  or a hydroxide ion  OH- , depending on the pH and the state of the enzyme.2. Activation of water molecule: The Zn2+ ion polarizes the coordinated water molecule, increasing its nucleophilic character and facilitating its deprotonation to form a hydroxide ion  OH- . This process is aided by a nearby glutamate residue, which acts as a proton shuttle, transferring the proton  H+  to a nearby water molecule or the bulk solvent.3. Nucleophilic attack: The activated hydroxide ion  OH-  acts as a nucleophile and attacks the electrophilic carbon atom of the carbon dioxide  CO2  molecule, which is positioned in the active site by a network of amino acid residues, including hydrophobic and polar interactions.4. Formation of bicarbonate ion: The nucleophilic attack results in the formation of a bicarbonate ion  HCO3-  and the regeneration of the Zn2+-bound water molecule. The newly formed bicarbonate ion is then released from the enzyme's active site, allowing another CO2 molecule to enter and undergo the same catalytic process.In summary, the metal ion  Zn2+  in the active site of carbonic anhydrase plays a crucial role in the enzyme's function by activating a water molecule, facilitating the nucleophilic attack on the CO2 molecule, and stabilizing the transition state during the formation of the bicarbonate ion. This allows carbonic anhydrase to efficiently catalyze the hydration of carbon dioxide to bicarbonate ion, which is essential for various physiological processes, including pH regulation, respiration, and CO2 transport in living organisms.

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