Summary for clan CD

Summary Structure Literature
Clan type peptidaseC14.001 - caspase-1 (Homo sapiens), MEROPS Accession MER0000850 (peptidase unit: 120-404); PDB accession 1ICE
HistoryPerspect.Drug Discov.Des. 6:1-11 (1996)
DescriptionCysteine nucleophile; catalytic residues in the order His, Cys in sequence
Contents of clanClan CD contains eight families of endopeptidases.
EvidenceClan CD contains families with a protein fold or sequence motifs similar to those found in the caspase family (C14). All families contain a His, Cys catalytic dyad. The catalytic His occurs in a His-Gly motif and is preceded by a block of hydrophobic residues; the catalytic Cys occurs in the motif Ala-Cys and is preceded by a second block of hydrophobic residues (Chen et al., 1998).
Catalytic mechanismThe His, Cys catalytic dyad acts with a mechanism distinct from the Cys, His dyads in clan CA (Polgar, 2004).
Peptidase activitySpecificity is strongly directed to the P1 residue of the substrate, which is normally Asn in family C13, Asp in family C14, and Arg (or sometimes Lys) in C11, C25 and C50. Glycosylphosphatidylinositol:protein transamidase (C13.005) is not a conventional endopeptidase, requiring removal of a C-terminal peptide before it can attach glycosylphosphatidylinositol anchors to newly synthesised proteins in the endoplasmic reticulum.
Protein foldTertiary structures have been determined for members of families C14 (Walker et al., 1994) and C25 (Eichinger et al., 1999). These show alpha/beta proteins with a fold that consists of an alpha/beta/alpha sandwich. The beta sheet contains six strands (in the order 213456) and strand 6 is antiparallel to the rest. Other families are included in the clan because of the conservation of motifs around the catalytic residues (Chen et al., 1998).
Homologous non-peptidase familiesThe fold is unique to members of clan CD.
Activation mechanismClan CD members are activated in a number of different ways. Peptidases in family C11 are synthesised as proenzymes and require removal of an N-terminal propeptide for activation (Labrou & Rigden, 2004). Peptidases in families C14 are activated by dimerization without proteolysis or by internal limited proteolysis (Boatright & Salvesen, 2003). Prolegumain (C13.004) activates itself by cleavage of an asparaginyl bond in the acidic conditions of the lysosome (Chen et al., 2000). Ginginpains R (C25.001) and K (C25.002) are secreted and work together to autolytically remove their C-terminal haemaglutinin domain.
Other databases PFAM'CL0093'


Family Family Type Peptidase Structure
C11 clostripain (Clostridium histolyticum) -
C13 legumain (plant beta form) (Canavalia ensiformis) Yes
C14 caspase-1 (Rattus norvegicus) Yes
C25 gingipain RgpA (Porphyromonas gingivalis) Yes
C50 separase (yeast-type) (Saccharomyces cerevisiae) -
C80 RTX self-cleaving toxin (Vibrio cholerae) Yes
C84 prtH peptidase ({Tannerella forsythensis} ATCC 43037) (Tannerella forsythia) -

Distribution of clan CD among Kingdoms of Organisms