Convergent carbonic anhydrase

A third family, the -carbonic anhydrases, also has been identified, initially in the archaeon Methanosarcina thermophila. The crystal structure of this enzyme reveals three zinc sites extremely similar to those in the a-carbonic anhydrases. In this case, however, the three zinc sites lie at the interfaces between the three subunits of a trimeric enzyme (Figure 9.31). The very striking left-handed P-helix (a P strand twisted into a left-handed helix) structure present in this enzyme has also been found in enzymes that catalyze reactions unrelated to those of carbonic anhydrase. Thus, convergent evolution has generated carbonic anhydrases that rely on coordinated zinc ions at least three times. In each case, the catalytic activity appears to be associated with zinc-bound water molecules. 

A study of spinach carbonic anhydrase showed very similar kinetic behavior, but also showed that the Zn is boimd to a sulfur atom. It was concluded that the two enzymes are convergently evolved, with different structures, but have equivalent functions. 

Convergent Evolution Has Generated Zinc-Based Active Sites in Different Carbonic Anhydrases... 

Convergent evolution has yielded three different classes of carbonic anhydrases. Mammals contain a-CA, plants and certain bacterial contain p-CA, while archea contain y-CA. The three classes of carbonic anhydrases differ in amino acid sequence and in their protein fold. Nevertheless, the active sites all contain a zinc ion (held by three histidine residues in the a- and y-CA, and by one histidine and two cysteines in the P-CA) and a hydrogen bond donor near the zinc and presumably catalyze the reaction in a similar manner. 

The other structural classes of carbonic anhydrases may also serve as protein ligands. The active site of the 3-CA is the approximate mirror image of that for a-CA. Nature s substrates, carbon dioxide and biocarbonate, are achiral so this mirror-image relationship is only an accident of convergent evolution. However, for enantioselective reactions, these two enzymes may form an enantiocomplementary pair and may catalyze reactions with opposite enantioselectivity. 

Using the carbonic anhydrases as examples, describe why convergent evolution is thought to have selected a common active-site structure. 

---