Protein superfamily

The term protein clan is commonly used for protease and glycosyl hydrolases superfamilies based on the MEROPS and CAZy classification systems.

Since some of the amino acids have similar properties (e.g., charge, hydrophobicity, size), conservative mutations that interchange them are often neutral to function.

In the PA clan of proteases, for example, not a single residue is conserved through the superfamily, not even those in the catalytic triad.

[6] In the absence of structural information, sequence similarity constrains the limits of which proteins can be assigned to a superfamily.

[10] However, on rare occasions, related proteins may evolve to be structurally dissimilar[11] and relatedness can only be inferred by other methods.

[12][13][14] The catalytic mechanism of enzymes within a superfamily is commonly conserved, although substrate specificity may be significantly different.

[16] For the families within the PA clan of proteases, although there has been divergent evolution of the catalytic triad residues used to perform catalysis, all members use a similar mechanism to perform covalent, nucleophilic catalysis on proteins, peptides or amino acids.

[15][21] Protein superfamilies represent the current limits of our ability to identify common ancestry.

A sequence alignment of mammalian histone proteins. The similarity of the sequences implies that they evolved by gene duplication . Residues that are conserved across all sequences are highlighted in grey. Below the protein sequences is a key denoting: [ 4 ]
Structural homology in the PA superfamily (PA clan). The double β-barrel that characterises the superfamily is highlighted in red. Shown are representative structures from several families within the PA superfamily. Note that some proteins show partially modified structural. Chymotrypsin (1gg6), tobacco etch virus protease (1lvm), calicivirin (1wqs), west nile virus protease (1fp7), exfoliatin toxin (1exf), HtrA protease (1l1j), snake venom plasminogen activator (1bqy), chloroplast protease (4fln) and equine arteritis virus protease (1mbm).