Folding Patterns and Protein Families

This barrel can be compared with that of the 12-helix a, a barrel of a fungal glucoamylase whose structure is shown in Fig. 2-29. Numerous more complex folding patterns have been discovered. They have been classified by Jane Richardson.117 122 Many of the proteins described by these folding patterns can be grouped into families and "superfamilies."227 Chothia suggested that there may be about 1,000 families in nature 268 over 700, with over 360 distinct folds have been identified.2683... 

Although the comparisons of protein folds can yield valuable insights into protein function and evolution, it is also very desirable to be able to detect structural similarities at the residue or atomic level. This is because the detection of similar patterns of functional groups in different proteins may allow analogies to be drawn between disparate proteins modes of action. The classic example of this are the similar clusters of three catalytic residues in the otherwise unrelated subtilisin and chymotrypsin families of enzymes [82]. 

The pattern of exons and introns (exon-intron-exon-intron-exon) in the a and /3 families of genes is quite old and apparently developed before the separation of these genes some 500 million years ago. The role of introns is unknown, although their base sequences vary. Because the introns are not transcribed, the protein sequences are unchanged. The introns appear to correspond to structural domains within the folded globulin subunits and are requisite for the posttranscriptional processing of mRNA. 

Crystal structures have been determined for both Fe and Mn SODs. These constitute a family of closely related proteins with homologous folding patterns. There is complete conservation of both the metal ligands and the aromatic residues surrounding the metal atom. The metal site has... 

The criterion for attributing a particular family name to a new structure is a property of protein tertiary structure that invites systematization and has come to known as the fold. The inflexibility of the polypeptide chain and side chain interactions imposes restriction on the limitation of favorable folding patterns for secondary structures to form tertiary structures. 

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