PA clan of proteases

[1][2] PA clan proteases can be found in plants,[3] animals,[3] fungi,[3] eubacteria,[4] archaea[5][6] and viruses.

[7] The differences in the catalytic triad within the PA clan is also an example of divergent evolution of active sites in enzymes.

[2][10][11] Based on structural homology, a superfamily was defined and later named the PA clan (by the MEROPS classification system).

Members of the PA clan can be found in eukaryotes, prokaryotes and viruses and encompass a wide range of functions.

Several snake venoms are also PA clan proteases, such as pit viper haemotoxin and interfere with the victim's blood clotting cascade.

Additionally, bacteria such as Staphylococcus aureus secrete exfoliative toxin which digest and damage the host's tissues.

[19][20] There are also several pseudoenzymes in the superfamily, where the catalytic triad residues have been mutated and so function as binding proteins.

Surface structure of TEV protease. The C-terminal extension only present in viral members of the PA clan of chymotrypsin-like proteases as (a) surface with loop in blue (b) secondary structure and (c) b-factor putty (wider regions indicate greater flexibility) for the structure of TEV protease. Substrate in black, active site triad in red. The final 15 amino acids (222-236) of the enzyme C-terminus are not visible in the structure as they are too flexible. ( PDB : 1lvm , 1lvb ​)
Evolutionary divergence of the catalytic triads to use different nucleophiles. Shown are the serine triad of chymotrypsin ( clan PA , family S1) and the cysteine triad of TEV protease ( clan PA , family C3).