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What is the coordination chemistry behind the catalytic activity of the metalloenzyme carbonic anhydrase, and how does the geometry of the active site play a crucial role in its function?

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Carbonic anhydrase  CA  is a metalloenzyme that plays a crucial role in the reversible hydration of carbon dioxide  CO2  to bicarbonate  HCO3-  and a proton  H+ . The catalytic activity of carbonic anhydrase is mainly attributed to the presence of a zinc ion  Zn2+  at its active site.The coordination chemistry of the active site in carbonic anhydrase involves the zinc ion being coordinated to three histidine residues  His  in a trigonal bipyramidal geometry. The fourth coordination site of the zinc ion is occupied by a water molecule  H2O  or a hydroxide ion  OH-  depending on the pH of the environment. The zinc ion acts as a Lewis acid, polarizing the bound water molecule and facilitating the nucleophilic attack on the CO2 molecule.The geometry of the active site plays a crucial role in the function of carbonic anhydrase. The trigonal bipyramidal geometry of the zinc coordination allows for optimal interaction between the zinc ion, the coordinating histidine residues, and the water molecule or hydroxide ion. This arrangement ensures that the zinc ion can effectively polarize the water molecule, making it more nucleophilic and capable of attacking the CO2 molecule.Additionally, the active site of carbonic anhydrase is surrounded by hydrophobic amino acid residues, which create a hydrophobic pocket that helps to stabilize the CO2 molecule and facilitate its interaction with the zinc-bound water molecule or hydroxide ion. This hydrophobic environment also helps to exclude other solvent molecules, ensuring that the reaction occurs specifically between the CO2 and the zinc-bound water molecule or hydroxide ion.In summary, the coordination chemistry and geometry of the active site in carbonic anhydrase are crucial for its catalytic activity. The zinc ion, coordinated in a trigonal bipyramidal geometry with three histidine residues and a water molecule or hydroxide ion, facilitates the nucleophilic attack on the CO2 molecule. The hydrophobic pocket surrounding the active site further stabilizes the CO2 and ensures the specificity of the reaction.

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