Principles of Protein Structure - G. Schultz 1982

Protein Evolution
Gene Fusion
Convergent Protein Evolution

The number of possible Amino acid sequences and chain-Folding Pathways is so vast that similarities cannot be regarded as random occurrences; clearly, they reflect historical development, i.e., the specialization or differentiation of Proteins. However, the immense number of structural variants does not rule out the possibility that certain structures are particularly favored and that specific Evolutionary Processes may converge toward them. Clear Examples of convergence in Cell/13.html">Protein Structure are α-helices and β-pleated sheets; this may apply to Supersecondary structures as well.

Evolutionary convergence of diverse structures toward a common function is quite common. Since a function can be performed in various ways, different proteins may acquire The ability to carry out similar Functions; their evolutionary pathways converge with respect to protein function. An example is the Reversible Binding of O₂ to Hemoglobin, hemerythrin*, and hemocyanin*. The O₂ molecule always binds to iron or copper, whose ions are incorporated into completely different protein structures [594]. Similar instances of structural convergence toward a common function have been noted for Mn²⁺-containing superoxide dismutases and Cu²⁺–Zn²⁺-containing superoxide dismutases [546, 595].

Classic examples of the results of convergent evolution are the catalytic centers of the Serine proteases Chymotrypsin and subtilisin [18, 239, 240]. Both Enzymes, upon interaction with a substrate, feature an identical arrangement of Hydrogen Bonds that anchor the main chain of the substrate, an identical position of the pocket accommodating side chains, the exact same charge-Relay mechanism for bond Cleavage, and the same set of Hydrogen bond Donors (backbone NH groups) that stabilize the carbonyl oxygen atoms of the catalytic intermediate [537]. Despite all this, the two enzymes show no correlation whatsoever in their amino acid sequences, chain folding, or, for instance, the numbering of the Asp, His, and Ser residues [18, 239, 240] within the charge-relay system.

* These names originate from the Greek word haima (Blood); they do not imply that the proteins necessarily contain a heme group.

Thus, it is precisely the refinement of the catalytic surfaces of chymotrypsin and subtilisin that led to their adoption of an identical function. As shown in Fig. 11.1, The Mechanism of catalytic action of the proteases Papain and glyceraldehyde-3-phosphate dehydrogenase, an enzyme of The Glycolytic Pathway, appears to be analogous to that of serine proteases. However, other pathways of polypeptide chain cleavage also exist, as seen in the examples of Thermolysin, cathepsins, and acidic proteases [539, 596].

Structural details of homologous Proteins can be the result of convergent evolution. During the subsequent evolution of proteins from a common ancestor, certain aspects of convergent evolution regarding the overall architecture of these Proteins can also be identified [273, 597]. For example, in the short variant of cytochrome c₅₅₁, a deeply buried propionic acid group of the heme is hydrogen-bonded to Trp-56, whereas in the long variant of mitochondrial cytochrome c, it is bonded to Trp-59* [509]. In this case, functionally important Trp residues occupy non-equivalent positions in homologous polypeptide chains. This demonstrates that modeling amino acid sequences by fixing the positions of functional residues can lead to erroneous Conclusions.

* The indicated Trp residues occupy non-homologous positions in the chains; the numbering schemes in the two Cytochromes were not aligned as in the schemes of Fig. 7.1a. The Trp residue in question corresponds to Trp-62 (Fig. 7.8).