Evolutionary lines of cysteine peptidases

The proteolytic enzymes that depend upon a cysteine residue for activity ha ve come from at least seven different evolutionary origins, each of which h as produced a group of cysteine peptidases with distinctive structures and properties. We show here that the characteristic molecular topologies of th e peptidases in each evolutionary line can be seen not only in their three- dimensional structures, but commonly also in the two-dimensional structures , Clan CA contains the families of papain (C1), calpain (C2), streptopain ( C10) and the ubiquitin-specific peptidases (C12, C19), as well as many fami lies of viral cysteine endopeptidases, Clan CD contains the families of clo stripain (C11), gingipain R (C25), legumain (C13), caspase-1 (C14) and sepa rin (C50), These enzymes have specificities dominated by the interactions o f the S1 subsite. Clan CE contains the families of adenain (C5) from adenov iruses, the eukaryotic Ulp1 protease (C48) and the bacterial YopJ proteases (C55), Clan CF contains only pyroglutamyl peptidase I(C15), The picornains (C3) in dan PA have probably evolved from serine peptidases, which still f orm the majority of enzymes in the dan. The cysteine peptidase activities i n clans PB and CH are autolytic only, In conclusion, we suggest that althou gh almost all the cysteine peptidases depend for activity on catalytic dyad s of cysteine and histidine, it is worth noting some important differences that they have inherited from their distant ancestral peptidases.