Evolution of structure in γ-class carbonic anhydrase and structurally related proteins

Protein structure contains evolutionary information and it is more highly conserved than sequence. The evolution of structure in γ-class carbonic anhydrase (γ-CA) and its structurally related proteins (γCASRPs) were discussed. To obtain a reliable analysis, we defined a subset that contains all specificities and organisms as the nonredundant set using QR factorization based on the multiple structural alignment of the known crystallographic structures of γCASRPs with QH as the structural homology measure. Then, we applied unweighted pair group method with arithmetic averages (UPGMA) to reconstruct structural phylogeny. We found that γ-CA most likely arose through duplication events; the domain of γ-CA underwent a process of α-helical content from amino-terminal end to carboxyl-terminal end of the left-handed β-helix (LβH); the capacity of γ-CA to bind Zn occurred early in evolution and only later included the ability to catalyze the reversible hydration of CO2 efficiently for the occurrence of two loops involving Glu 62 and Glu 84, respectively, and a long helix at the carboxyl-terminal end of the LβH. In addition, the main conserved regions in these structures are in the structurally constrained residues of LβH domain, and the topology of the structural dendrogram can be rather easily understood in terms of functional diversification.