Genes pepsin

AA 2 Families of endopeptidases (including pepsin, renin and some cathepsins in family Al) and several other families Asp Two lobes from separate genes... 

Aspartic peptidases have so far been described for all endopeptidases. Unfortunately, the tertiary structure has only been elucidated for four families. Endopeptidases of the family A1 consist of two lobes, with the active site between them. One lobe has been derived from the other by gene duplication. In the active site each lobe, with very similar three-dimensional structures, bears one Asp residue of the catalytic dyad. It is interesting to note that the crystal structure of retropepsin from family A2 of clan AA showed a single lobe with one catalytic Asp residue with structural similarity to one lobe of the pepsin from family Al. Retropepsin is only active as a homodimer forming the catalytic site between the two monomeric molecules. There is evidence that the peptidases of families Al and A2 have evolved from a common ancestor. Unfortunately, a number of other families could not yet been assigned to any clan. 

An archaebacterial acid protease (optimum pH 2.0) which may represent a new class of enzyme has been purified recently from Sulfolobus acidocaldarius [297, 298]. Although the specificity of the enzyme was similar to pepsin, with preference shown towards bonds between large hydrophobic residues, inhibitor studies indicated differences in active site composition. Furthermore, the nucleotide sequence of the enzyme gene was completely dissimilar to those for enzymes of the pepsin family and to pepstatin-insensitive acid protease. 

In acid proteases, which are also organized in two topologically similar domains, there is a remarkable internal homology which indicates that these enzymes have evolved by gene duplication of an ancestral protein of about 150 residues having a fold similar to one domain of pepsin (Tang et aL, 1978 Subramanian et al, 1977). 

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