CARBONIC ANHYDRASE

The protein carbonic anhydrase catalyses the formation of bicarbonate ion from carbon dioxide and water:

H2O + CO2 ---> (HCO3)- + H+

Part of the catalytic enhancement of the reaction is due to the Zn2+ ion that is coordinated to three histidine amino acid residues in the enzyme that hold the ion in position. The Zn2+ is also coordinated to a water molecule.

The carbonic anhydrase peptide chain is shown as a molecular model in its "ribbon" display emphasizing the coordination of zinc ion with the histidine side chains in the cleft of the active site. Here is a close-in view of the active site coordination between Zn2+ ion and the histidine rings.

This is a Lewis structure of the same active site, also shown with a coordinated water molecule. What is/are the specific intermolecular forces of attraction that account for the zinc coordination to histidine and water?

The attraction of the zinc ion for the oxygen electrons in the water molecule induces a further polarization of the O-H bonds and makes the H more positive than it would be without coordination to the zinc.  What is this effect called?

The proton (H)+ is transferred from water to another amino acid residue (not shown) and the resulting OH- ion attacks the CO2 to form bicarbonate (in a reaction we will study in carbonyl chemistry).

H2O  ---> (OH)-  +  (H)+                               CO2  +  (OH)-  --->  (HOCO2)-

In what capacity is the amino acid residue (not shown) acting? In what capacities are the carbon dioxide and hydroxide ions acting? [Choose from: Bronsted-Lowry acid, Bronsted-Lowry base, Lewis acid, or Lewis base.]

See also Solomons & Fryle, p. 1119.

Answers

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Answers:

The zinc is a cation, which would be attracted to negative charges/non-bonded electrons. Both histidine and water have non-bonded electrons on electronegative atoms (N, O). These atoms are the negative ends of dipoles. So the interactions are ion-dipole.

 

Inductive effect

 

Amino acid residue is accepting a proton so it is a base (Bronsted-Lowry). The hydroxide is an electron-pair donor (Lewis base) and the C in O=C=O, which is quite positive, is the electron pair acceptor (Lewis acid). A new covalent bond is formed HO-CO2-. Note that these latter two cannot be Bronsted-Lowry acids or bases since no proton is exchanged.