Summary for clan CP

Summary Alignment Structure Literature
DescriptionCysteine nucleophile; catalytic residues in the order His, Cys in sequence
Contents of clanPeptidase clan CP contains isopeptidases.
EvidenceThe existence of a group of proteins predicted to have a circularly permuted papain-like structure was first postulated by Iyer et al., 2004. These were predicted to have deubiquitinylating functions because of the presence of domains similar to ubiquitin-binding domains. These proteins were collectively known as the PPPDE superfamily, for 'permuted papain fold peptidases of dsRNA viruses and eukaryotes'.
Catalytic mechanismA catalytic dyad consisting of His and Cys (in that order in the sequence) has been identified from the solved tertiary structure of the DeSI-1 peptidase. This is in the reverse order to that found in papain (C01.001). Another difference from members of clan CA is that no third active site residue is required to orientate the histidine ring (Su et al. 2012, ). The highly conserved Asp15, which had been predicted to be part of a catalytic triad (Iyer et al., 2004), appears to be structurally important, but it does not interact with the catalytic His (Suh et al., 2012).
Peptidase activityAll characterized members of clan CP are isopeptidases, releasing SUMO from polySUMOylated proteins (%Shin et al., 2012[20120311A174]%>).
Protein foldThe fold determined for DeSI-1 has several similarities to that of papain. For example, the active site Cys is at the N-terminal end of a helix, and the active site His is on a strand that is part of a beta-barrel (Su et al. 2012, ).
EvolutionAlthough it has been suggested that members of the clans CP and CA are evolutionarily related, no similarity between members of the two clans can be detected using the DALI algorithm and server (Holm & Sander, 1995). Instead, members of clan CO are structurally related to members of clan CP, and it would be more accurate to describe members of clan CP to have permuted forms of the CO-like fold.
Homologous non-peptidase familiesThe tertiary structures of two other proteins have been solved and show similar folds: the YiiX protein from Escherichia coli (PDB 2IF6) and the BCE_A0238 protein from Bacillus cereus (Xu etal, 2011). Unfortunately, neither of these proteins has been biochemically characterized and it not known if they they are peptidases or not.

Families

Family Family Type Peptidase Structure
C97 DeSI-1 peptidase (Mus musculus) Yes

Distribution of clan CP among Kingdoms of Organisms

FamilyBacteriaArchaeaProtozoaFungiPlantsAnimalsViruses
C97+-+++++
Clan+-+++++