page_title: PA clan of proteases
section_title: Catalytic activity
hierarchical_section_title: PA clan of proteases / Evolution and function / Catalytic activity
caption_attribution_description: English: 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).
context_page_description: The PA clan is the largest group of proteases with common ancestry as identified by structural homology. Members have a chymotrypsin-like fold and similar proteolysis mechanisms but can have identity of <10%. The clan contains both cysteine and serine proteases. PA clan proteases can be found in plants, animals, fungi, eubacteria, archaea and viruses.
  The common use of the catalytic triad for hydrolysis by multiple clans of proteases, including the PA clan, represents an example of convergent evolution. The differences in the catalytic triad within the PA clan is also an example of divergent evolution of active sites in enzymes.
context_section_description: Structural homology indicates that the PA clan members are descended from a common ancestor of the same fold. Although PA clan proteases use a catalytic triad perform 2-step nucleophilic catalysis, some families use serine as the nucleophile whereas others use cysteine. The superfamily is therefore an extreme example of divergent enzyme evolution since during evolutionary history, the core catalytic residue of the enzyme has switched in different families. In addition to their structural similarity, directed evolution has been shown to be able to convert a cysteine protease into an active serine protease. All cellular PA clan proteases are serine proteases, however there are both serine and cysteine protease families of viral proteases. The majority are endopeptidases, with the exception being the S46 family of exopeptidases.
caption: 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).
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